Bio


Dr. Melissa Bondy is the inaugural chair of the Department of Epidemiology and Population Health and the Associate Director for Population Sciences at the Stanford Cancer Institute. Before joining Stanford, she was Associate Director of Cancer Prevention and Population Sciences and section chair of Epidemiology and Population Sciences at Baylor College of Medicine. Her research focus is in genetic and molecular epidemiology and is at the forefront of developing innovative ways to assess the roles of heredity and genetic susceptibility in the etiology of cancer and outcomes, primarily brain and breast cancer. Currently, she leads the largest family study of glioma patients, as well as a study of molecular predictors of outcome for glioma patients. She has a strong interest in health disparities and has a current study to investigate the ethnic differences in glioma. She has been working on studying the health effects of exposure to Hurricane Harvey. She serves on the National Cancer Institute’s (NCI) Board of Scientific Advisors, where she provides direct counsel to the Director of the NCI, and is a member of the External Advisory Board for several NCI-designated cancer centers. In 2018, she received the Visiting Scholar Award from the NCI Division of Cancer Epidemiology and Genetics.

Academic Appointments


Administrative Appointments


  • Chair, Department of Epidemiology and Population Health, Stanford University School of Medicine (2019 - Present)
  • Co-Director, Stanford Center for Population Health Sciences (2019 - Present)
  • Associate Director, Population Sciences at the Stanford Cancer Institute (2019 - Present)
  • Professor of Epidemiology, Department of Epidemiology, The University of Texas, School of Public Health (2002 - Present)

Honors & Awards


  • Visiting Scholar Award, National Cancer Institute Division of Cancer Epidemiology and Genetics (2018)
  • Michael O’Malley Distinguished Professor Award, University of North Carolina (2020)

Boards, Advisory Committees, Professional Organizations


  • COVID-19 Clinical Research Review Panel, School of Medicine, Stanford University (2020 - Present)
  • Respond, Recover, Re-open [R3] Team, School of Medicine, Stanford University (2020 - Present)
  • School of Medicine’s Executive Committee, Stanford University (2019 - Present)
  • Stanford Cancer Institute Executive Committee, Stanford University (2019 - Present)
  • External Advisory Board, UK Markey Cancer Center (2020 - Present)
  • External Advisory Board, University of Chicago Cancer Center (2020 - Present)
  • External Advisory Committee, University of Hawaii Cancer Center (2019 - Present)
  • External Advisory Board, Masonic Cancer Center, University of Minnesota (2018 - Present)
  • External Advisory Board, University of Mississippi Cancer Center (2017 - Present)
  • External Scientific Advisory Board, The University of Minnesota Cancer Center Member (2005 - Present)
  • External Advisor, Successfully Obtain Comprehensive Status (2004 - Present)
  • Susan G. Komen Scientific Director, Susan G. Komen Share For Cures Study (2019 - Present)
  • External Advisory Board, Fred Hutchinson Cancer Center (2020 - Present)
  • External Advisory Board, University of Chicago Cancer Center (2019 - Present)
  • External Advisory Board, Rutgers Cancer Institute of New Jersey (2019 - Present)
  • External Advisory Committee, Multi-Ethnic Cohort, University of Hawaii (2018 - Present)
  • Board of Scientific Advisors, National Cancer Institute (2016 - Present)
  • TRSS-Glioblastoma Working Group, National Cancer Institute (2018 - Present)
  • NCI Board of Scientific Advisors, Subcommittee on Global Cancer Research (2014 - Present)
  • Center Scientific Advisory Board, University of Washington EDGE (2014 - Present)
  • Advisory Committee, Duke Cancer Institute External Scientific (2011 - Present)
  • External Advisor, Childhood Cancer Survivors Study - St. Jude Children’s Hospital, Memphis, TN (2009 - Present)
  • Review Editor, Frontiers in Applied Genetic Epidemiology, Frontiers (2011 - Present)
  • Honorary Editorial Board, The Application of Clinical Genetics (2008 - Present)
  • Senior Editor, Cancer Epidemiology, Biomarkers & Prevention (2008 - Present)
  • Editorial Board, Molecular and Translational Epidemiology (2007 - Present)

Current Research and Scholarly Interests


Principal Investigator, Discovery, Biology and Risk of Inherited Variants in Glioma, 1R01CA217105-01A1, NIH/NCI, 05/01/2018-06/30/2022, MPI (Contact PI)

Principal Investigator, Characterizing Germline and Somatic Alterations by Glioma Subtypes and Clinical Outcome, 1R01CA232754-01, 07/01/2019-06/30/2023, MPI (Contact PI)

Co-Leader (Project), SPORE in Brain Cancer, PI – Fred Lang (Sub with MD Anderson), 2 P50CA127001-11, 09/01/2019-08/31/2023

Co-Investigator, Stanford University Cancer Center, PI – Steve Artandi, P30 CA124435, NCI, 09/15/10-05/31/22

Co-Investigator, Ovarian Cancer Survival in African-American Women, PI, Joellen Schildkraut, R01 CA237318-01A1, NIH/NCI, 07/01/2020-06/31/2025

2020-21 Courses


All Publications


  • Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers. Nature communications Zhang, Y. D., Hurson, A. N., Zhang, H., Choudhury, P. P., Easton, D. F., Milne, R. L., Simard, J., Hall, P., Michailidou, K., Dennis, J., Schmidt, M. K., Chang-Claude, J., Gharahkhani, P., Whiteman, D., Campbell, P. T., Hoffmeister, M., Jenkins, M., Peters, U., Hsu, L., Gruber, S. B., Casey, G., Schmit, S. L., O'Mara, T. A., Spurdle, A. B., Thompson, D. J., Tomlinson, I., De Vivo, I., Landi, M. T., Law, M. H., Iles, M. M., Demenais, F., Kumar, R., MacGregor, S., Bishop, D. T., Ward, S. V., Bondy, M. L., Houlston, R., Wiencke, J. K., Melin, B., Barnholtz-Sloan, J., Kinnersley, B., Wrensch, M. R., Amos, C. I., Hung, R. J., Brennan, P., McKay, J., Caporaso, N. E., Berndt, S. I., Birmann, B. M., Camp, N. J., Kraft, P., Rothman, N., Slager, S. L., Berchuck, A., Pharoah, P. D., Sellers, T. A., Gayther, S. A., Pearce, C. L., Goode, E. L., Schildkraut, J. M., Moysich, K. B., Amundadottir, L. T., Jacobs, E. J., Klein, A. P., Petersen, G. M., Risch, H. A., Stolzenberg-Solomon, R. Z., Wolpin, B. M., Li, D., Eeles, R. A., Haiman, C. A., Kote-Jarai, Z., Schumacher, F. R., Al Olama, A. A., Purdue, M. P., Scelo, G., Dalgaard, M. D., Greene, M. H., Grotmol, T., Kanetsky, P. A., McGlynn, K. A., Nathanson, K. L., Turnbull, C., Wiklund, F., Breast Cancer Association Consortium (BCAC), Barretts and Esophageal Adenocarcinoma Consortium (BEACON), Colon Cancer Family Registry (CCFR), Transdisciplinary Studies of Genetic Variation in Colorectal Cancer (CORECT), Endometrial Cancer Association Consortium (ECAC), Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Melanoma Genetics Consortium (GenoMEL), Glioma International Case-Control Study (GICC), International Lung Cancer Consortium (ILCCO), Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium, International Consortium of Investigators Working on Non-Hodgkins Lymphoma Epidemiologic Studies (InterLymph), Ovarian Cancer Association Consortium (OCAC), Oral Cancer GWAS, Pancreatic Cancer Case-Control Consortium (PanC4), Pancreatic Cancer Cohort Consortium (PanScan), Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL), Renal Cancer GWAS, Testicular Cancer Consortium (TECAC), Chanock, S. J., Chatterjee, N., Garcia-Closas, M., Easton, D. F., Milne, R. L., Simard, J., Hall, P., Michailidou, K., Dennis, J., Schmidt, M. K., Chang-Claude, J., Gharahkhani, P., Whiteman, D., Campbell, P. T., Hoffmeister, M., Jenkins, M., Peters, U., Hsu, L., Gruber, S. B., Casey, G., Schmit, S. L., Campbell, P. T., Hoffmeister, M., Jenkins, M., Peters, U., Hsu, L., Gruber, S. B., Casey, G., Schmit, S. L., O'Mara, T. A., Spurdle, A. B., Thompson, D. J., Tomlinson, I., De Vivo, I., Campbell, P. T., Hoffmeister, M., Jenkins, M., Peters, U., Hsu, L., Gruber, S. B., Casey, G., Schmit, S. L., Landi, M. T., Law, M. H., Iles, M. M., Demenais, F., Kumar, R., MacGregor, S., Bishop, D. T., Ward, S. V., Bondy, M. L., Houlston, R., Wiencke, J. K., Melin, B., Barnholtz-Sloan, J., Kinnersley, B., Wrensch, M. R., Amos, C. I., Hung, R. J., Brennan, P., McKay, J., Caporaso, N. E., Amos, C. I., Hung, R. J., Brennan, P., McKay, J., Caporaso, N. E., Berndt, S. I., Birmann, B. M., Camp, N. J., Kraft, P., Rothman, N., Slager, S. L., Berchuck, A., Pharoah, P. D., Sellers, T. A., Gayther, S. A., Pearce, C. L., Goode, E. L., Schildkraut, J. M., Moysich, K. B., Amos, C. I., Brennan, P., McKay, J., Amundadottir, L. T., Jacobs, E. J., Klein, A. P., Petersen, G. M., Risch, H. A., Stolzenberg-Solomon, R. Z., Wolpin, B. M., Li, D., Amundadottir, L. T., Jacobs, E. J., Klein, A. P., Petersen, G. M., Risch, H. A., Stolzenberg-Solomon, R. Z., Wolpin, B. M., Li, D., Eeles, R. A., Haiman, C. A., Kote-Jarai, Z., Schumacher, F. R., Al Olama, A. A., Purdue, M. P., Scelo, G., Dalgaard, M. D., Greene, M. H., Grotmol, T., Kanetsky, P. A., McGlynn, K. A., Nathanson, K. L., Turnbull, C., Wiklund, F. 2020; 11 (1): 3353

    Abstract

    Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.

    View details for DOI 10.1038/s41467-020-16483-3

    View details for PubMedID 32620889

  • European genetic ancestry associated with risk of childhood ependymoma. Neuro-oncology Zhang, C., Ostrom, Q. T., Hansen, H. M., Gonzalez-Maya, J., Hu, D., Ziv, E., Morimoto, L., de Smith, A. J., Muskens, I. S., Kline, C. N., Vaksman, Z., Hakonarson, H., Diskin, S. J., Kruchko, C., Barnholtz-Sloan, J. S., Ramaswamy, V., Ali-Osman, F., Bondy, M. L., Taylor, M. D., Metayer, C., Wiemels, J. L., Walsh, K. M. 2020

    Abstract

    BACKGROUND: Ependymoma is a histologically defined central nervous system tumor most commonly occurring in childhood. Population-level incidence differences by race/ethnicity are observed, with individuals of European ancestry at highest risk. We aimed to determine whether extent of European genetic ancestry is associated with ependymoma risk in US populations.METHODS: In a multi-ethnic study of Californian children (327 cases, 1970 controls), we estimated the proportions of European, African, and Native American ancestry among recently admixed Hispanic and African American subjects and estimated European admixture among non-Hispanic white subjects using genome-wide data. We tested whether genome-wide ancestry differences were associated with ependymoma risk and performed admixture mapping to identify associations with local ancestry. We also evaluated race/ethnicity-stratified ependymoma incidence data from the Central Brain Tumor Registry of the United States (CBTRUS).RESULTS: CBTRUS data revealed that African American and Native American children have 33% and 36%, respectively, reduced incidence of ependymoma compared with non-Hispanic whites. In genetic analyses, a 20% increase in European ancestry was associated with a 1.31-fold higher odds of ependymoma among self-reported Hispanics and African Americans (95% CI: 1.08-1.59, Pmeta = 6.7 * 10-3). Additionally, eastern European ancestral substructure was associated with increased ependymoma risk in non-Hispanic whites (P = 0.030) and in Hispanics (P = 0.043). Admixture mapping revealed a peak at 20p13 associated with increased local European ancestry, and targeted fine-mapping identified a lead variant at rs6039499 near RSPO4 (odds ratio = 1.99; 95% CI: 1.45-2.73; P = 2.2 * 10-5) but which was not validated in an independent set of posterior fossa type A patients.CONCLUSIONS: Interethnic differences in ependymoma risk are recapitulated in the genomic ancestry of ependymoma patients, implicating regions to target in future association studies.

    View details for DOI 10.1093/neuonc/noaa130

    View details for PubMedID 32607579

  • Modernizing Population Sciences in the Digital Age. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Wang, S. S., Goodman, M. T., Bondy, M. 2020; 29 (4): 712–13

    View details for DOI 10.1158/1055-9965.EPI-20-0268

    View details for PubMedID 32238400

  • Lack of association between modifiable exposures and glioma risk: a Mendelian randomization analysis NEURO-ONCOLOGY Saunders, C. N., Cornish, A. J., Kinnersley, B., Law, P. J., Claus, E. B., Il'yasova, D., Schildkraut, J., Barnholtz-Sloan, J. S., Olson, S. H., Bernstein, J. L., Lai, R. K., Chanock, S., Rajaraman, P., Johansen, C., Jenkins, R. B., Melin, B. S., Wrensch, M. R., Sanson, M., Bondy, M. L., Houlston, R. S. 2020; 22 (2): 207–15

    Abstract

    The etiological basis of glioma is poorly understood. We have used genetic markers in a Mendelian randomization (MR) framework to examine if lifestyle, cardiometabolic, and inflammatory factors influence the risk of glioma. This methodology reduces bias from confounding and is not affected by reverse causation.We identified genetic instruments for 37 potentially modifiable risk factors and evaluated their association with glioma risk using data from a genome-wide association study of 12 488 glioma patients and 18 169 controls. We used the estimated odds ratio of glioma associated with each of the genetically defined traits to infer evidence for a causal relationship with the following exposures:Lifestyle and dietary factors-height, plasma insulin-like growth factor 1, blood carnitine, blood methionine, blood selenium, blood zinc, circulating adiponectin, circulating carotenoids, iron status, serum calcium, vitamins (A1, B12, B6, E, and 25-hydroxyvitamin D), fatty acid levels (monounsaturated, omega-3, and omega-6) and circulating fetuin-A;Cardiometabolic factors-birth weight, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, total triglycerides, basal metabolic rate, body fat percentage, body mass index, fasting glucose, fasting proinsulin, glycated hemoglobin levels, diastolic and systolic blood pressure, waist circumference, waist-to-hip ratio; andInflammatory factors- C-reactive protein, plasma interleukin-6 receptor subunit alpha and serum immunoglobulin E.After correction for the testing of multiple potential risk factors and excluding associations driven by one single nucleotide polymorphism, no significant association with glioma risk was observed (ie, PCorrected > 0.05).This study did not provide evidence supporting any of the 37 factors examined as having a significant influence on glioma risk.

    View details for DOI 10.1093/neuonc/noz209

    View details for Web of Science ID 000518531900008

    View details for PubMedID 31665421

  • Glioma risk associated with extent of estimated European genetic ancestry in African Americans and Hispanics INTERNATIONAL JOURNAL OF CANCER Ostrom, Q. T., Egan, K. M., Nabors, L., Gerke, T., Thompson, R. C., Olson, J. J., LaRocca, R., Chowdhary, S., Eckel-Passow, J. E., Armstrong, G., Wiencke, J. K., Bernstein, J. L., Claus, E. B., Il'yasova, D., Johansen, C., Lachance, D. H., Lai, R. K., Merrell, R. T., Olson, S. H., Sadetzki, S., Schildkraut, J. M., Shete, S., Houlston, R. S., Jenkins, R. B., Wrensch, M. R., Melin, B., Amos, C. I., Huse, J. T., Barnholtz-Sloan, J. S., Bondy, M. L. 2020; 146 (3): 739–48

    Abstract

    Glioma incidence is highest in non-Hispanic Whites, and to date, glioma genome-wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk. We assessed whether EA was associated with glioma in African Americans and Hispanics. Data were obtained for 832 cases and 675 controls from the Glioma International Case-Control Study and GliomaSE Case-Control Study previously estimated to have <80% EA, or self-identify as non-White. We estimated global and local ancestry using fastStructure and RFMix, respectively, using 1,000 genomes project reference populations. Within groups with ≥40% AA (AFR≥0.4 ), and ≥15% NAA (AMR≥0.15 ), genome-wide association between local EA and glioma was evaluated using logistic regression conditioned on global EA for all gliomas. We identified two regions (7q21.11, p = 6.36 × 10-4 ; 11p11.12, p = 7.0 × 10-4 ) associated with increased EA, and one associated with decreased EA (20p12.13, p = 0.0026) in AFR≥0.4 . In addition, we identified a peak at rs1620291 (p = 4.36 × 10-6 ) in 7q21.3. Among AMR≥0.15 , we found an association between increased EA in one region (12q24.21, p = 8.38 × 10-4 ), and decreased EA in two regions (8q24.21, p = 0. 0010; 20q13.33, p = 6.36 × 10-4 ). No other significant associations were identified. This analysis identified an association between glioma and two regions previously identified in EA populations (8q24.21, 20q13.33) and four novel regions (7q21.11, 11p11.12, 12q24.21 and 20p12.13). The identifications of novel association with EA suggest regions to target for future genetic association studies.

    View details for DOI 10.1002/ijc.32318

    View details for Web of Science ID 000531411900016

    View details for PubMedID 30963577

  • POT1 mutation spectrum in tumour types commonly diagnosed among POT1-associated hereditary cancer syndrome families. Journal of medical genetics Shen, E., Xiu, J., Lopez, G. Y., Bentley, R., Jalali, A., Heimberger, A. B., Bainbridge, M. N., Bondy, M. L., Walsh, K. M. 2020

    Abstract

    BACKGROUND: The shelterin complex is composed of six proteins that protect and regulate telomere length, including protection of telomeres 1 (POT1). Germline POT1 mutations are associated with an autosomal dominant familial cancer syndrome presenting with diverse malignancies, including glioma, angiosarcoma, colorectal cancer and melanoma. Although somatic POT1 mutations promote telomere elongation and genome instability in chronic lymphocytic leukaemia, the contribution of POT1 mutations to development of other sporadic cancers is largely unexplored.METHODS: We performed logistic regression, adjusted for tumour mutational burden, to identify associations between POT1 mutation frequency and tumour type in 62368 tumours undergoing next-generation sequencing.RESULTS: A total of 1834 tumours harboured a non-benign mutation of POT1 (2.94%), of which 128 harboured a mutation previously reported to confer familial cancer risk in the setting of germline POT1 deficiency. Angiosarcoma was 11 times more likely than other tumours to harbour a POT1 mutation (p=1.4*10-20), and 65% of POT1-mutated angiosarcoma had >1 mutations in POT1. Malignant gliomas were 1.7 times less likely to harbour a POT1 mutation (p=1.2*10-3) than other tumour types. Colorectal cancer was 1.2 times less likely to harbour a POT1 mutation (p=0.012), while melanoma showed no differences in POT1 mutation frequency versus other tumours (p=0.67).CONCLUSIONS: These results confirm a role for shelterin dysfunction in angiosarcoma development but suggest that gliomas arising in the context of germline POT1 deficiency activate a telomere-lengthening mechanism that is uncommon in gliomagenesis.

    View details for DOI 10.1136/jmedgenet-2019-106657

    View details for PubMedID 31937561

  • US Public Concerns About the COVID-19 Pandemic From Results of a Survey Given via Social Media. JAMA internal medicine Nelson, L. M., Simard, J. F., Oluyomi, A., Nava, V., Rosas, L. G., Bondy, M., Linos, E. 2020

    View details for DOI 10.1001/jamainternmed.2020.1369

    View details for PubMedID 32259192

  • The Genetic Architecture of Gliomagenesis-Genetic Risk Variants Linked to Specific Molecular Subtypes. Cancers Wu, W. Y., Johansson, G., Wibom, C., Brannstrom, T., Malmstrom, A., Henriksson, R., Golovleva, I., Bondy, M. L., Andersson, U., Dahlin, A. M., Melin, B. 2019; 11 (12)

    Abstract

    Genome-wide association studies have identified 25 germline genetic loci that increase the risk of glioma. The somatic tumor molecular alterations, including IDH-mutation status and 1p/19q co-deletion, have been included into the WHO 2016 classification system for glioma. To investigate how the germline genetic risk variants correlate with the somatic molecular subtypes put forward by WHO, we performed a meta-analysis that combined findings from 330 Swedish cases and 876 controls with two other recent studies. In total, 5,103 cases and 10,915 controls were included. Three categories of associations were found. First, variants in TERT and TP53 were associated with increased risk of all glioma subtypes. Second, variants in CDKN2B-AS1, EGFR, and RTEL1 were associated with IDH-wildtype glioma. Third, variants in CCDC26 (the 8q24 locus), C2orf80 (close to IDH), LRIG1, PHLDB1, ETFA, MAML2 and ZBTB16 were associated with IDH-mutant glioma. We therefore propose three etiopathological pathways in gliomagenesis based on germline variants for future guidance of diagnosis and potential functional targets for therapies. Future prospective clinical trials of patients with suspicion of glioma diagnoses, using the genetic variants as biomarkers, are necessary to disentangle how strongly they can predict glioma diagnosis.

    View details for DOI 10.3390/cancers11122001

    View details for PubMedID 31842352

  • CLINICAL PREDICTIVE MODEL FOR THE DEVELOPMENT OF VENOUS THROMBOEMBOLISM IN GLIOBLASTOMA Yust-Katz, S., Donthireddy, V., Mandel, J., Abunafeesa, H., Patil, N., Yadav, D., Jabbour-Aida, H., Wu, J., Yuan, Y., Tsavachidis, S., Walbert, T., Bondy, M., Armstrong, T. OXFORD UNIV PRESS INC. 2019: 204
  • Risk factors for childhood and adult primary brain tumors NEURO-ONCOLOGY Ostrom, Q. T., Fahmideh, M., Cote, D. J., Muskens, I. S., Schraw, J. M., Scheurer, M. E., Bondy, M. L. 2019; 21 (11): 1357–75

    Abstract

    Primary brain tumors account for ~1% of new cancer cases and ~2% of cancer deaths in the United States; however, they are the most commonly occurring solid tumors in children. These tumors are very heterogeneous and can be broadly classified into malignant and benign (or non-malignant), and specific histologies vary in frequency by age, sex, and race/ethnicity. Epidemiological studies have explored numerous potential risk factors, and thus far the only validated associations for brain tumors are ionizing radiation (which increases risk in both adults and children) and history of allergies (which decreases risk in adults). Studies of genetic risk factors have identified 32 germline variants associated with increased risk for these tumors in adults (25 in glioma, 2 in meningioma, 3 in pituitary adenoma, and 2 in primary CNS lymphoma), and further studies are currently under way for other histologic subtypes, as well as for various childhood brain tumors. While identifying risk factors for these tumors is difficult due to their rarity, many existing datasets can be leveraged for future discoveries in multi-institutional collaborations. Many institutions are continuing to develop large clinical databases including pre-diagnostic risk factor data, and developments in molecular characterization of tumor subtypes continue to allow for investigation of more refined phenotypes. Key Point 1. Brain tumors are a heterogeneous group of tumors that vary significantly in incidence by age, sex, and race/ethnicity.2. The only well-validated risk factors for brain tumors are ionizing radiation (which increases risk in adults and children) and history of allergies (which decreases risk).3. Genome-wide association studies have identified 32 histology-specific inherited genetic variants associated with increased risk of these tumors.

    View details for DOI 10.1093/neuonc/noz123

    View details for Web of Science ID 000496767300007

    View details for PubMedID 31301133

    View details for PubMedCentralID PMC6827837

  • ROLE OF POT1 MUTATION IN GLIOMA PROLIFERATION AND SEXUAL DIVERGENCE OF SURVIVAL Jalali, A., Yu, K., Beechar, V., Mehra, D., Lozzi, B., Bondy, M., Deneen, B. OXFORD UNIV PRESS INC. 2019: 102
  • Perceived discrimination, trust in physicians, and prolonged symptom duration before ovarian cancer diagnosis in the African American Cancer Epidemiology Study CANCER Mullins, M. A., Peres, L. C., Alberg, A. J., Bandera, E., Barnholtz-Sloan, J. S., Bondy, M. L., Funkhouser, E., Moorman, P. G., Peters, E. S., Terry, P. D., Schwartz, A. G., Lawson, A. B., Schildkraut, J. M., Cote, M. L. 2019; 125 (24): 4442–51

    Abstract

    Discrimination and trust are known barriers to accessing health care. Despite well-documented racial disparities in the ovarian cancer care continuum, the role of these barriers has not been examined. This study evaluated the association of everyday discrimination and trust in physicians with a prolonged interval between symptom onset and ovarian cancer diagnosis (hereafter referred to as prolonged symptom duration).Subjects included cases enrolled in the African American Cancer Epidemiology Study, a multisite case-control study of epithelial ovarian cancer among black women. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of everyday discrimination and trust in physicians with a prolonged symptom duration (1 or more symptoms lasting longer than the median symptom-specific duration), and it controlled for access-to-care covariates and potential confounders.Among the 486 cases in this analysis, 302 women had prolonged symptom duration. In the fully adjusted model, a 1-unit increase in the frequency of everyday discrimination increased the odds of prolonged symptom duration 74% (OR, 1.74; 95% CI, 1.22-2.49), but trust in physicians was not associated with prolonged symptom duration (OR, 0.86; 95% CI, 0.66-1.11).Perceived everyday discrimination was associated with prolonged symptom duration, whereas more commonly evaluated determinants of access to care and trust in physicians were not. These results suggest that more research on the effects of interpersonal barriers affecting ovarian cancer care is warranted.

    View details for DOI 10.1002/cncr.32451

    View details for Web of Science ID 000481154100001

    View details for PubMedID 31415710

    View details for PubMedCentralID PMC6891111

  • Previously identified common glioma risk SNPs are associated with familial glioma Ostrom, Q. T., Armstrong, G., Amos, C. I., Bernstein, J. L., Claus, E. B., Eckel-Passow, J. E., Il'yasova, D., Johansen, C., Lachance, D. H., Lai, R. K., Merrell, R. T., Olson, S. H., Schildkraut, J. H., Shete, S. S., Houlston, R. S., Jenkins, R. B., Wrensch, M. R., Melin, B., Barnholtz-Sloan, J. S., Bondy, M. L. AMER ASSOC CANCER RESEARCH. 2019
  • Mendelian randomisation study of the relationship between vitamin D and risk of glioma (vol 8, 2339, 2018) SCIENTIFIC REPORTS Takahashi, H., Cornish, A. J., Sud, A., Law, P. J., Kinnersley, B., Ostrom, Q., Labreche, K., Eckel-Passow, J. E., Armstrong, G. N., Claus, E. B., Il'yasova, D., Schildkraut, J., Barnholtz-Sloan, J. S., Olson, S. H., Bernstein, J. L., Lai, R. K., Schoemaker, M. J., Simon, M., Hoffmann, P., Noethen, M. M., Joeckel, K., Chanock, S., Rajaraman, P., Johansen, C., Jenkins, R. B., Melin, B. S., Wrensch, M. R., Sanson, M., Bondy, M. L., Turnbull, C., Houlston, R. S. 2019; 9: 7924

    Abstract

    A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

    View details for DOI 10.1038/s41598-019-43787-2

    View details for Web of Science ID 000468772000001

    View details for PubMedID 31118477

    View details for PubMedCentralID PMC6531429

  • Integrating germline and somatic genomic analysis to probe etiological mechanism in malignant glioma. Oncotarget Ostrom, Q., Bondy, M. L., Huse, J. T. 2019; 10 (33): 3086–87

    View details for DOI 10.18632/oncotarget.26897

    View details for PubMedID 31139320

  • Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women CANCER MEDICINE Grant, D. J., Manichaikul, A., Alberg, A. J., Bandera, E., Barnholtz-Sloan, J., Bondy, M., Cote, M. L., Funkhouser, E., Moorman, P. G., Peres, L. C., Peters, E. S., Schwartz, A. G., Terry, P. D., Wang, X., Keku, T. O., Hoyo, C., Berchuck, A., Sandler, D. P., Taylor, J. A., O'Brien, K. M., Edwards, D., Edwards, T. L., Beeghly-Fadiel, A., Wentzensen, N., Pearce, C., Wu, A. H., Whittemore, A. S., McGuire, V., Sieh, W., Rothstein, J. H., Modugno, F., Ness, R., Moysich, K., Rossing, M., Doherty, J. A., Sellers, T. A., Permuth-Way, J. B., Monteiro, A. N., Levine, D. A., Setiawan, V., Haiman, C. A., LeMarchand, L., Wilkens, L. R., Karlan, B. Y., Menon, U., Ramus, S., Gayther, S., Gentry-Maharaj, A., Terry, K. L., Cramer, D. W., Goode, E. L., Larson, M. C., Kaufmann, S. H., Cannioto, R., Odunsi, K., Etter, J. L., Huang, R., Bernardini, M. Q., Tone, A. A., May, T., Goodman, M. T., Thompson, P. J., Carney, M. E., Tworoger, S. S., Poole, E. M., Lambrechts, D., Vergote, I., Vanderstichele, A., Van Nieuwenhuysen, E., Anton-Culver, H., Ziogas, A., Brenton, J. D., Bjorge, L., Salvensen, H. B., Kiemeney, L. A., Massuger, L. G., Pejovic, T., Bruegl, A., Moffitt, M., Cook, L., Le, N. D., Brooks-Wilson, A., Kelemen, L. E., Pharoah, P. P., Song, H., Campbe, I., Eccles, D., DeFazio, A., Kennedy, C. J., Schildkraut, J. M. 2019; 8 (5): 2503–13

    View details for DOI 10.1002/cam4.1996

    View details for Web of Science ID 000469272500052

  • Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma CANCER RESEARCH Atkins, I., Kinnersley, B., Ostrom, Q. T., Labreche, K., Il'yasova, D., Armstrong, G. N., Eckel-Passow, J. E., Schoemaker, M. J., Nothen, M. M., Barnholtz-Sloan, J. S., Swerdlow, A. J., Simon, M., Rajaraman, P., Chanock, S. J., Shildkraut, J., Bernstein, J. L., Hoffman, P., Jockel, K., Lai, R. K., Claus, E. B., Olson, S. H., Johansen, C., Wrensch, M. R., Melin, B., Jenkins, R. B., Sanson, M., Bondy, M. L., Houlston, R. S. 2019; 79 (8): 2065–71

    Abstract

    Genome-wide association studies (GWAS) have so far identified 25 loci associated with glioma risk, with most showing specificity for either glioblastoma (GBM) or non-GBM tumors. The majority of these GWAS susceptibility variants reside in noncoding regions and the causal genes underlying the associations are largely unknown. Here we performed a transcriptome-wide association study to search for novel risk loci and candidate causal genes at known GWAS loci using Genotype-Tissue Expression Project (GTEx) data to predict cis-predicted gene expression in relation to GBM and non-GBM risk in conjunction with GWAS summary statistics on 12,488 glioma cases (6,183 GBM and 5,820 non-GBM) and 18,169 controls. Imposing a Bonferroni-corrected significance level of P < 5.69 × 10-6, we identified 31 genes, including GALNT6 at 12q13.33, as a candidate novel risk locus for GBM (mean Z = 4.43; P = 5.68 × 10-6). GALNT6 resides at least 55 Mb away from any previously identified glioma risk variant, while all other 30 significantly associated genes were located within 1 Mb of known GWAS-identified loci and were not significant after conditioning on the known GWAS-identified variants. These data identify a novel locus (GALNT6 at 12q13.33) and 30 genes at 12 known glioma risk loci associated with glioma risk, providing further insights into glioma tumorigenesis. SIGNIFICANCE: This study identifies new genes associated with glioma risk, increasing understanding of how these tumors develop.

    View details for DOI 10.1158/0008-5472.CAN-18-2888

    View details for Web of Science ID 000464651500032

    View details for PubMedID 30709929

  • Using germline variants to estimate glioma and subtype risks NEURO-ONCOLOGY Eckel-Passow, J. E., Decker, P. A., Kosel, M. L., Kollmeyer, T. M., Molinaro, A. M., Rice, T., Caron, A. A., Drucker, K. L., Praska, C. E., Pekmezci, M., Hansen, H. M., McCoy, L. S., Bracci, P. M., Erickson, B. J., Lucchinetti, C. F., Wiemels, J. L., Wiencke, J. K., Bondy, M. L., Melin, B., Burns, T. C., Giannini, C., Lachance, D. H., Wrensch, M. R., Jenkins, R. B. 2019; 21 (4): 451–61

    Abstract

    Twenty-five single nucleotide polymorphisms (SNPs) are associated with adult diffuse glioma risk. We hypothesized that the inclusion of these 25 SNPs with age at diagnosis and sex could estimate risk of glioma as well as identify glioma subtypes.Case-control design and multinomial logistic regression were used to develop models to estimate the risk of glioma development while accounting for histologic and molecular subtypes. Case-case design and logistic regression were used to develop models to predict isocitrate dehydrogenase (IDH) mutation status. A total of 1273 glioma cases and 443 controls from Mayo Clinic were used in the discovery set, and 852 glioma cases and 231 controls from UCSF were used in the validation set. All samples were genotyped using a custom Illumina OncoArray.Patients in the highest 5% of the risk score had more than a 14-fold increase in relative risk of developing an IDH mutant glioma. Large differences in lifetime absolute risk were observed at the extremes of the risk score percentile. For both IDH mutant 1p/19q non-codeleted glioma and IDH mutant 1p/19q codeleted glioma, the lifetime risk increased from almost null to 2.3% and almost null to 1.7%, respectively. The SNP-based model that predicted IDH mutation status had a validation concordance index of 0.85.These results suggest that germline genotyping can provide new tools for the initial management of newly discovered brain lesions. Given the low lifetime risk of glioma, risk scores will not be useful for population screening; however, they may be useful in certain clinically defined high-risk groups.

    View details for DOI 10.1093/neuonc/noz009

    View details for Web of Science ID 000462632100006

    View details for PubMedID 30624711

    View details for PubMedCentralID PMC6422428

  • Effect of health disparities on overall survival of patients with glioblastoma JOURNAL OF NEURO-ONCOLOGY Mandel, J. J., Youssef, M., Nam, J., Patel, A. J., Jalali, A., Ludmir, E. B., Liu, D., Wu, J., Armstrong, G., Huse, J., Bondy, M., de Groot, J. F. 2019; 142 (2): 365–74

    Abstract

    Examine the potential effects of health disparities in survival of glioblastoma (GB) patients.We conducted a retrospective chart review of newly diagnosed GB patients from 2000 to 2015 at a free standing dedicated cancer center (MD Anderson Cancer Center-MDACC) and a safety net county hospital (Ben Taub General Hospital-BT) located in Houston, Texas. We obtained demographics, insurance status, extent of resection, treatments, and other known prognostic variables (Karnofsky Score-KPS) to evaluate their role on overall GB survival (OS).We identified 1073 GB patients consisting of 177 from BT and 896 from MDACC. We found significant differences by ethnicity, insurance status, KPS at diagnosis, extent of resection, and percentage of patients receiving standard of care (SOC) between the two centers. OS was 1.64 years for MDACC patients and 1.24 years for BT patients (p < 0.0176). Only 81 (45.8%) BT patients received SOC compared to 577 (64%) of MDACC patients (p < 0.0001). However, there was no significant difference in OS for patients who received SOC, 1.84 years for MDACC patients and 1.99 years for BT patients (p < 0.4787). Of the 96 BT patients who did not receive SOC, 29 (30%) had KPS less than 70 at time of diagnosis and 77 (80%) lacked insurance.GB patients treated at a safety net county hospital had similar OS compared to a free standing comprehensive cancer center when receiving SOC. County hospital patients had poorer KPS at diagnosis and were often lacking health insurance affecting their ability to receive SOC.

    View details for DOI 10.1007/s11060-019-03108-z

    View details for Web of Science ID 000463662100018

    View details for PubMedID 30671709

  • Aspirin, NSAIDs, and Glioma Risk: Original Data from the Glioma International Case-Control Study and a Meta-analysis CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Amirian, E., Ostrom, Q. T., Armstrong, G. N., Lai, R. K., Gu, X., Jacobs, D. I., Jalali, A., Claus, E. B., Barnholtz-Sloan, J. S., Il'yasova, D., Schildkraut, J. M., Ali-Osman, F., Sadetzki, S., Jenkins, R. B., Lachance, D. H., Olson, S. H., Bernstein, J. L., Merrell, R. T., Wrensch, M. R., Johansen, C., Houlston, R. S., Scheurer, M. E., Shete, S., Amos, C. I., Melin, B., Bondy, M. L. 2019; 28 (3): 555–62

    Abstract

    There have been few studies of sufficient size to address the relationship between glioma risk and the use of aspirin or NSAIDs, and results have been conflicting. The purpose of this study was to examine the associations between glioma and aspirin/NSAID use, and to aggregate these findings with prior published studies using meta-analysis.The Glioma International Case-Control Study (GICC) consists of 4,533 glioma cases and 4,171 controls recruited from 2010 to 2013. Interviews were conducted using a standardized questionnaire to obtain information on aspirin/NSAID use. We examined history of regular use for ≥6 months and duration-response. Restricted maximum likelihood meta-regression models were used to aggregate site-specific estimates, and to combine GICC estimates with previously published studies.A history of daily aspirin use for ≥6 months was associated with a 38% lower glioma risk, compared with not having a history of daily use [adjusted meta-OR = 0.62; 95% confidence interval (CI), 0.54-0.70]. There was a significant duration-response trend (P = 1.67 × 10-17), with lower ORs for increasing duration of aspirin use. Duration-response trends were not observed for NSAID use. In the meta-analysis aggregating GICC data with five previous studies, there was a marginally significant association between use of aspirin and glioma (mOR = 0.84; 95% CI, 0.70-1.02), but no association for NSAID use.Our study suggests that aspirin may be associated with a reduced risk of glioma.These results imply that aspirin use may be associated with decreased glioma risk. Further research examining the association between aspirin use and glioma risk is warranted.

    View details for DOI 10.1158/1055-9965.EPI-18-0702

    View details for Web of Science ID 000465326400017

    View details for PubMedID 30482874

    View details for PubMedCentralID PMC6401283

  • Targetable Immune Regulatory Molecule Expression in High-Grade Serous Ovarian Carcinomas in African American Women: A Study of PD-L1 and IDO in 112 Cases From the African American Cancer Epidemiology Study (AACES) INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY Mills, A. M., Peres, L. C., Meiss, A., Ring, K. L., Modesitt, S. C., Abbott, S. E., Alberg, A. J., Bandera, E. V., Barnholtz-Sloan, J., Bondy, M. L., Cote, M. L., Funkhouser, E., Moorman, P. G., Peters, E. S., Schwartz, A. G., Terry, P. D., Wallace, K., Schildkraut, J. M. 2019; 38 (2): 157–70

    Abstract

    African American women with high-grade serous ovarian carcinoma have worse outcomes compared with women of European descent. Although the discrepancy is partially attributed to differences in access to care, the tumor immune microenvironment may also contribute. Expression of targetable immune regulatory molecules such as programmed cell death ligand-1 (PD-L1) and indoleamine 2,3 dioxygenase (IDO) is of particular interest as it may help guide therapy in this population. Using cases from the largest study of African American women with ovarian cancer, the African American Cancer Epidemiology Study, we characterized PD-L1 and IDO expression in 112 high-grade serous ovarian carcinomas. Immunohistochemistry for PD-L1, IDO, CD8, FOX3p, and CD68 was performed. PD-L1 and IDO were scored as the percentage of positive tumor cells and tumor-associated immune cells. CD8 and FOX3p counts were averaged across 10 high-power fields. Cox proportional hazards regression was used to evaluate the association between PD-L1 and IDO expression and survival. Tumor cells were positive for PD-L1 and IDO in 29% and 58% of cases, respectively. The majority showed <10% staining, and no cases exceeded 25% positivity. The majority of PD-L1-positive cases coexpressed IDO. PD-L1 and IDO expression was associated with higher CD8 and FOX3p counts (P<0.05). No association was observed between PD-L1 and IDO and survival. In summary, expression of PD-L1 and IDO is seen in a subset of high-grade serous ovarian carcinoma from African American women and is correlated with elevated lymphocyte infiltration. While PD-L1 and IDO co-expression suggests a role for dual immunotherapy, diffuse expression of PD-L1 and IDO is rare, invoking caution regarding the potential for immunotherapeutic response.

    View details for DOI 10.1097/PGP.0000000000000494

    View details for Web of Science ID 000459155700007

    View details for PubMedID 29485423

    View details for PubMedCentralID PMC6109628

  • Cumulative copy number imbalances after neoadjuvant chemotherapy residual breast tumor is an independent predictor of relapse Thompson, P. A., Brewster, A., Tsavachidis, S., Armstrong, G., Do, K., Ha, M., Gutierrez, C., Symmans, F., Bondy, M. AMER ASSOC CANCER RESEARCH. 2019
  • A Mixed-Methods Study to Examine the Role of Psychosocial Stress and Air Pollution on Hypertension in Mexican-Origin Hispanics JOURNAL OF RACIAL AND ETHNIC HEALTH DISPARITIES Rammah, A., Whitworth, K., Han, I., Chan, W., Jimenez, M. D., Strom, S. S., Bondy, M. L., Symanski, E. 2019; 6 (1): 12–21

    Abstract

    Independent and combined effects of air pollution and psychosocial stressors on hypertension, a risk factor for cardiovascular disease, among Hispanics are not well studied.We administered a pilot-tested questionnaire on individual- and neighborhood-level psychosocial stressors, developed with community input, to nearly 2500 individuals from the MD Anderson Cancer Center cohort of Mexican-Americans. We used data from local air quality monitors to estimate individual exposures to ozone (O3) and fine particulate matter (PM2.5) for the 12-month period preceding enrollment using inverse distance interpolation. We applied logistic regression models to examine relationships between exposures to psychosocial stressors and air pollution with prevalent hypertension and used stratified analyses to examine the interacting effects of these two exposures on hypertension. RESULTS: There was a positive association between prevalent hypertension and a high frequency of feeling anxious or depressed (prevalence odds ratio (POR) = 1.36, 95% CI [1.06-1.75]) and experiencing aches and pains (POR = 1.29, 95% CI [1.01-1.64]). The odds of having hypertension were also elevated among those worrying about their own health (POR = 1.65, 95% CI [1.30-2.06]) or about not having enough money (POR = 1.27, 95% CI [1.01-1.6]). We observed an inverse association between O3 and hypertension. There was no interaction between psychosocial stressors and O3 on hypertension.Our findings add to the evidence of a positive association between individual and family stressors on hypertension among Hispanics and other racial/ethnic groups. Contrary to previous studies reporting positive associations, our results suggest that long-term exposure to O3 may be inversely related to prevalent hypertension.

    View details for DOI 10.1007/s40615-018-0490-1

    View details for Web of Science ID 000457419900002

    View details for PubMedID 29679333

    View details for PubMedCentralID PMC6347581

  • Mendelian randomization provides support for obesity as a risk factor for meningioma SCIENTIFIC REPORTS Takahashi, H., Cornish, A. J., Sud, A., Law, P. J., Disney-Hogg, L., Calvocoressi, L., Lu, L., Hansen, H. M., Smirnov, I., Walsh, K. M., Schramm, J., Hoffmann, P., Noethen, M. M., Joeckel, K., Schildkraut, J. M., Simon, M., Bondy, M., Wrensch, M., Wiemels, J. L., Claus, E. B., Turnbull, C., Houlston, R. S. 2019; 9: 309

    Abstract

    Little is known about the causes of meningioma. Obesity and obesity-related traits have been reported in several epidemiological observational studies to be risk factors for meningioma. We performed an analysis of genetic variants associated with obesity-related traits to assess the relationship with meningioma risk using Mendelian randomization (MR), an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. We considered 11 obesity-related traits, identified genetic instruments for these factors, and assessed their association with meningioma risk using data from a genome-wide association study comprising 1,606 meningioma patients and 9,823 controls. To evaluate the causal relationship between the obesity-related traits and meningioma risk, we consider the estimated odds ratio (OR) of meningioma for each genetic instrument. We identified positive associations between body mass index (odds ratio [ORSD] = 1.27, 95% confidence interval [CI] = 1.03-1.56, P = 0.028) and body fat percentage (ORSD = 1.28, 95% CI = 1.01-1.63, P = 0.042) with meningioma risk, albeit non-significant after correction for multiple testing. Associations for basal metabolic rate, diastolic blood pressure, fasting glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, systolic blood pressure, total cholesterol, triglycerides and waist circumference with risk of meningioma were non-significant. Our analysis provides additional support for obesity being associated with an increased risk of meningioma.

    View details for DOI 10.1038/s41598-018-36186-6

    View details for Web of Science ID 000456282100064

    View details for PubMedID 30670737

    View details for PubMedCentralID PMC6343031

  • Longitudinal associations of family functioning with body mass index in Mexican-origin adolescents living in the U.S PREVENTIVE MEDICINE Heredia, N., Wilkinson, A., Forman, M. R., Christie, I. C., Wang, J., Daniel, C. R., Zhao, H., Bondy, M. L., Strong, L. L. 2019; 118: 309–16

    Abstract

    Mexican-origin adolescents have a high prevalence of obesity. Research is needed to understand how family context may shape adolescent BMI. This study examined longitudinal associations of family functioning variables with the Centers for Disease Control and Prevention's modified BMI z-score (BMIaz) in 1175 Mexican-origin adolescents, and explored interactions with acculturation. Adolescents (50% female, aged 11-13 y in 2005-06) were identified from an ongoing cohort study of Mexican-origin adults in Houston, TX, and were assessed three times from 2005-06 to 2010-11. In multivariate linear mixed models stratified by gender, we assessed longitudinal associations of family cohesion and family conflict with adolescent BMIaz and explored interactions with language acculturation. We disaggregated the between- (mean) and within-person (individual deviation) components of family cohesion and family conflict to assess the effects on BMIaz. Approximately one-third of adolescents were obese at baseline, and BMIaz declined during the study. In girls, higher mean family cohesion and conflict were associated with steeper declines in BMIaz. Parental linguistic acculturation modified the relationship between within-person deviation in family cohesion and BMIaz in girls, such that high parental U.S. acculturation was associated with a stronger inverse association. There were no significant associations in boys. These findings highlight the potential importance of the family context to female adolescent BMI and the promise of addressing family context in obesity-related interventions.

    View details for DOI 10.1016/j.ypmed.2018.11.009

    View details for Web of Science ID 000454933300044

    View details for PubMedID 30419254

    View details for PubMedCentralID PMC6467205

  • Identification of novel epithelial ovarian cancer loci in Women of African Ancestry. International journal of cancer Manichaikul, A., Peres, L. C., Wang, X. Q., Barnard, M. E., Chyn, D., Sheng, X., Du, Z., Tyrer, J., Dennis, J., Schwartz, A. G., Cote, M. L., Peters, E., Moorman, P. G., Bondy, M., Barnholtz-Sloan, J. S., Terry, P., Alberg, A. J., Bandera, E. V., Funkhouser, E., Wu, A. H., Pearce, C. L., Pike, M., Setiawan, V. W., Haiman, C. A., Palmer, J. R., LeMarchand, L., Wilkens, L. R., Berchuck, A., Doherty, J. A., Modugno, F., Ness, R., Moysich, K., Karlan, B. Y., Whittemore, A. S., McGuire, V., Sieh, W., Lawrenson, K., Gayther, S., Sellers, T. A., Pharoah, P., Schildkraut, J. M. 2019

    Abstract

    Women of African Ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European Ancestry. We conducted a genome-wide association study (GWAS) in African ancestry women with 755 EOC cases, including 537 high-grade serous ovarian carcinomas (HGSOC), and 1,235 controls. We identified four novel loci with suggestive evidence of association with EOC (P < 1x10-6 ), including rs4525119 (intronic to AKR1C3), rs7643459 (intronic to LOC101927394), rs4286604 (12 kb 3' of UGT2A2), and rs142091544 (5 kb 5' of WWC1). For HGSOC, we identified six loci with suggestive evidence of association including rs37792 (132 kb 5' of FST), rs57403204 (81 kb 3' of MAGEC1), rs79079890 (LOC105376360 intronic), rs66459581 (5 kb 5' of PRPSAP1), rs116046250 (GABRG3 intronic), and rs192876988 (32 kb 3' of GK2). Among the identified variants, two are near genes known to regulate hormones and diseases of the ovary (AKR1C3 and FST), and two are linked to cancer (AKR1C3 and MAGEC1). In follow-up studies of the 10 identified variants, the GK2 region SNP, rs192876988, showed an inverse association with EOC in European ancestry women (P = 0.002), increased risk of ER positive breast cancer in African ancestry women (P = 0.027), and decreased expression of GK2 in HGSOC tissue from African ancestry women (P = 0.004). A European ancestry-derived polygenic risk score showed positive associations with EOC and HGSOC in women of African ancestry suggesting shared genetic architecture. Our investigation presents evidence of variants for EOC shared among European and African ancestry women and identifies novel EOC risk loci in women of African ancestry. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/ijc.32653

    View details for PubMedID 31469419

  • Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women. Cancer medicine Grant, D. J., Manichaikul, A., Alberg, A. J., Bandera, E. V., Barnholtz-Sloan, J., Bondy, M., Cote, M. L., Funkhouser, E., Moorman, P. G., Peres, L. C., Peters, E. S., Schwartz, A. G., Terry, P. D., Wang, X. Q., Keku, T. O., Hoyo, C., Berchuck, A., Sandler, D. P., Taylor, J. A., O'Brien, K. M., Velez Edwards, D. R., Edwards, T. L., Beeghly-Fadiel, A., Wentzensen, N., Pearce, C. L., Wu, A. H., Whittemore, A. S., McGuire, V., Sieh, W., Rothstein, J. H., Modugno, F., Ness, R., Moysich, K., Rossing, M. A., Doherty, J. A., Sellers, T. A., Permuth-Way, J. B., Monteiro, A. N., Levine, D. A., Setiawan, V. W., Haiman, C. A., LeMarchand, L., Wilkens, L. R., Karlan, B. Y., Menon, U., Ramus, S., Gayther, S., Gentry-Maharaj, A., Terry, K. L., Cramer, D. W., Goode, E. L., Larson, M. C., Kaufmann, S. H., Cannioto, R., Odunsi, K., Etter, J. L., Huang, R. Y., Bernardini, M. Q., Tone, A. A., May, T., Goodman, M. T., Thompson, P. J., Carney, M. E., Tworoger, S. S., Poole, E. M., Lambrechts, D., Vergote, I., Vanderstichele, A., Van Nieuwenhuysen, E., Anton-Culver, H., Ziogas, A., Brenton, J. D., Bjorge, L., Salvensen, H. B., Kiemeney, L. A., Massuger, L. F., Pejovic, T., Bruegl, A., Moffitt, M., Cook, L., Le, N. D., Brooks-Wilson, A., Kelemen, L. E., Pharoah, P. D., Song, H., Campbell, I., Eccles, D., DeFazio, A., Kennedy, C. J., Schildkraut, J. M. 2019

    Abstract

    An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 1.2 × 10-6 , BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6-3.4, P = 1.6 × 10-5 , BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 2.3 × 10-5 , BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.

    View details for PubMedID 31001917

  • Sex-specific gene and pathway modeling of inherited glioma risk NEURO-ONCOLOGY Ostrom, Q. T., Coleman, W., Huang, W., Rubin, J. B., Lathia, J. D., Berens, M. E., Speyer, G., Liao, P., Wrensch, M. R., Eckel-Passow, J. E., Armstrong, G., Rice, T., Wiencke, J. K., McCoy, L. S., Hansen, H. M., Amos, C. I., Bernstein, J. L., Claus, E. B., Houlston, R. S., Il'yasova, D., Jenkins, R. B., Johansen, C., Lachance, D. H., Lai, R. K., Merrell, R. T., Olson, S. H., Sadetzki, S., Schildkraut, J. M., Shete, S., Andersson, U., Rajaraman, P., Chanock, S. J., Linet, M. S., Wang, Z., Yeager, M., Melin, B., Bondy, M. L., Barnholtz-Sloan, J. S., Freeman, L., Koutros, S., Albanes, D., Visvanathan, K., Stevens, V. L., Henriksson, R., Michaud, D. S., Feychting, M., Ahlbom, A., Giles, G. G., Giles, G. G., Milne, R., McKean-Cowdin, R., Le Marchand, L., Stampfer, M., Ruder, A. M., Carreon, T., Hallmans, G., Zeleniuch-Jacquotte, A., Gaziano, J., Sesso, H. D., Purdue, M. P., White, E., Peters, U., Buring, J., GliomaScan Consortium 2019; 21 (1): 71–82

    Abstract

    To date, genome-wide association studies (GWAS) have identified 25 risk variants for glioma, explaining 30% of heritable risk. Most histologies occur with significantly higher incidence in males, and this difference is not explained by currently known risk factors. A previous GWAS identified sex-specific glioma risk variants, and this analysis aims to further elucidate risk variation by sex using gene- and pathway-based approaches.Results from the Glioma International Case-Control Study were used as a testing set, and results from 3 GWAS were combined via meta-analysis and used as a validation set. Using summary statistics for nominally significant autosomal SNPs (P < 0.01 in a previous meta-analysis) and nominally significant X-chromosome SNPs (P < 0.01), 3 algorithms (Pascal, BimBam, and GATES) were used to generate gene scores, and Pascal was used to generate pathway scores. Results were considered statistically significant in the discovery set when P < 3.3 × 10-6 and in the validation set when P < 0.001 in 2 of 3 algorithms.Twenty-five genes within 5 regions and 19 genes within 6 regions reached statistical significance in at least 2 of 3 algorithms in males and females, respectively. EGFR was significantly associated with all glioma and glioblastoma in males only and a female-specific association in TERT, all of which remained nominally significant after conditioning on known risk loci. There were nominal associations with the BioCarta telomeres pathway in both males and females.These results provide additional evidence that there may be differences by sex in genetic risk for glioma. Additional analyses may further elucidate the biological processes through which this risk is conferred.

    View details for DOI 10.1093/neuonc/noy135

    View details for Web of Science ID 000462586300009

    View details for PubMedID 30124908

    View details for PubMedCentralID PMC6303471

  • Elucidating the molecular pathogenesis of glioma: integrated germline and somatic profiling of a familial glioma case series NEURO-ONCOLOGY Jacobs, D. I., Fukumura, K., Bainbridge, M. N., Armstrong, G. N., Tsavachidis, S., Gu, X., Doddapaneni, H. V., Hu, J., Jayaseelan, J. C., Muzny, D. M., Huse, J. T., Bondy, M. L. 2018; 20 (12): 1625–33

    Abstract

    The genomic characterization of sporadically arising gliomas has delineated molecularly and clinically distinct subclasses of disease. However, less is known about the molecular nature of gliomas that are familial in origin. We performed molecular subtyping of 163 tumor specimens from individuals with a family history of glioma and integrated germline and somatic genomic data to characterize the pathogenesis of 20 tumors in additional detail.Immunohistochemical analyses were performed on formalin-fixed, paraffin-embedded tumor sections to determine molecular subtypes of glioma. For 20 cases, tumor DNA was exome sequenced on an Illumina HiSeq 2000 platform and copy number profiling was performed on the Illumina HumanOmniExpress BeadChip. Genotypes at glioma risk polymorphisms were determined from germline DNA profiled on the Illumina Infinium OncoArray and deleterious germline mutations were identified from germline sequencing data.All 3 molecular subtypes of sporadic glioma were represented in the overall case series, including molecular glioblastoma (n = 102), oligodendroglioma (n = 21), and astrocytoma (n = 20). Detailed profiling of 20 of these cases showed characteristic subtype-specific alterations at frequencies comparable to sporadic glioma cases. All 20 cases had alterations in genes regulating telomere length. Frequencies of common glioma risk alleles were similar to those among sporadic cases, and correlations between risk alleles and same-gene somatic mutations were not observed.This study illustrates that the molecular characteristics of familial tumors profiled largely recapitulate what is known about sporadic glioma and that both germline and somatic molecular features target common core pathways involved in gliomagenesis.1. Familial and sporadic gliomas display highly comparable molecular landscapes. 2. Germline and somatic molecular events target common core pathways involved in gliomagenesis. 3. Carriage of germline glioma risk variants is not associated with somatic events in the same gene.

    View details for DOI 10.1093/neuonc/noy119

    View details for Web of Science ID 000452753300009

    View details for PubMedID 30165405

    View details for PubMedCentralID PMC6231201

  • Effect of Cultural, Folk, and Religious Beliefs and Practices on Delays in Diagnosis of Ovarian Cancer in African American Women JOURNAL OF WOMENS HEALTH Moorman, P. G., Barrett, N. J., Wang, F., Alberg, J., Bandera, E. V., Barnholtz-Sloan, J. B., Bondy, M., Cote, M. L., Funkhouser, E., Kelemen, L. E., Peres, L. C., Peters, E. S., Schwartz, A. G., Terry, P. D., Crankshaw, S., Abbott, S. E., Schildkraut, J. M. 2019; 28 (4): 444–51

    Abstract

    Certain cultural, folk, and religious beliefs that are more common among African Americans (AAs) have been associated with later-stage breast cancer. It is unknown if these beliefs are similarly associated with delays in diagnosis of ovarian cancer.Data from a multicenter case-control study of ovarian cancer in AA women were used to examine associations between cultural/folk beliefs and religious practices and stage at diagnosis and symptom duration before diagnosis. Associations between cultural/folk beliefs or religious practices and stage at diagnosis were assessed with logistic regression analyses, and associations with symptom duration with linear regression analyses.Agreement with several of the cultural/folk belief statements was high (e.g., 40% agreed that "if a person prays about cancer, God will heal it without medical treatments"), and ∼90% of women expressed moderate to high levels of religiosity/spirituality. Higher levels of religiosity/spirituality were associated with a twofold increase in the odds of stage III-IV ovarian cancer, whereas agreement with the cultural/folk belief statements was not associated with stage. Symptom duration before diagnosis was not consistently associated with cultural/folk beliefs or religiosity/spirituality.Women who reported stronger religious beliefs or practices had increased odds of higher stage ovarian cancer. Inaccurate cultural/folk beliefs about cancer treament were not associated with stage; however, these beliefs were highly prevalent in our population and could impact patient treatment decisions. Our findings suggest opportunities for health education interventions, especially working with churches, and improved doctor-patient communication.

    View details for DOI 10.1089/jwh.2018.7031

    View details for Web of Science ID 000451281100001

    View details for PubMedID 30481095

    View details for PubMedCentralID PMC6482889

  • Age-specific genome-wide association study in glioblastoma identifies increased proportion of 'lower grade glioma'-like features associated with younger age INTERNATIONAL JOURNAL OF CANCER Ostrom, Q. T., Kinnersley, B., Armstrong, G., Rice, T., Chen, Y., Wiencke, J. K., McCoy, L. S., Hansen, H. M., Amos, C. I., Bernstein, J. L., Claus, E. B., Eckel-Passow, J. E., Il'yasova, D., Johansen, C., Lachance, D. H., Lai, R. K., Merrell, R. T., Olson, S. H., Sadetzki, S., Schildkraut, J. M., Shete, S., Rubin, J. B., Andersson, U., Rajaraman, P., Chanock, S. J., Linet, M. S., Wang, Z., Yeager, M., Houlston, R. S., Jenkins, R. B., Wrensch, M. R., Melin, B., Bondy, M. L., Barnholtz-Sloan, J. S., GliomaScan Consortium 2018; 143 (10): 2359–66

    Abstract

    Glioblastoma (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age-at-diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age-at-diagnosis has been explored, genome-wide association studies (GWAS) have not previously been stratified by age. Potential age-specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18-53, 54-64, 65+) datasets were analyzed using age-stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta-analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p54-63 = 1.50x10-9 , OR54-63 = 1.28, 95%CI54-63 = 1.18-1.39; p64+ = 2.14x10-11 , OR64+ = 1.32, 95%CI64+ = 1.21-1.43] and rs11979158 [p54-63 = 6.13x10-8 , OR54-63 = 1.35, 95%CI54-63 = 1.21-1.50; p64+ = 2.18x10-10 , OR64+ = 1.42, 95%CI64+ = 1.27-1.58]) but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18-53 (p18-53 = 9.30 × 10-11 , OR18-53 = 1.76, 95%CI18-53 = 1.49-2.10). Within The Cancer Genome Atlas (TCGA) there was higher prevalence of 'LGG'-like tumor characteristics in GBM samples in those 18-53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54-63] and 0.8% [64+] (p = 0.0005). Age-specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18-53 suggests that more younger individuals may present initially with 'secondary glioblastoma.'

    View details for DOI 10.1002/ijc.31759

    View details for Web of Science ID 000450113100004

    View details for PubMedID 30152087

    View details for PubMedCentralID PMC6205887

  • PREVIOUSLY IDENTIFIED COMMON GLIOMA RISK SNPs ARE ASSOCIATED WITH FAMILIAL GLIOMA Ostrom, Q., Armstrong, G., Amos, C., Bernstein, J., Claus, E., Eckel-Passow, J., Il'yasova, D., Johansen, C., Lachance, D., Lai, R., Merrell, R., Olson, S., Schildkraut, J., Shete, S., Houlston, R., Jenkins, R., Wrensch, M., Melin, B., Barnholtz-Sloan, J., Bondy, M. OXFORD UNIV PRESS INC. 2018: 108
  • Genome-wide association analysis identifies a meningioma risk locus at 11p15.5 NEURO-ONCOLOGY Claus, E. B., Cornish, A. J., Broderick, P., Schildkraut, J. M., Dobbins, S. E., Holroyd, A., Calvocoressi, L., Lu, L., Hansen, H. M., Smirnov, I., Walsh, K. M., Schramm, J., Hoffmann, P., Nothen, M. M., Jockel, K., Swerdlow, A., Larsen, S., Johansen, C., Simon, M., Bondy, M., Wrensch, M., Houlston, R. S., Wiemels, J. L. 2018; 20 (11): 1485–93

    Abstract

    Meningiomas are adult brain tumors originating in the meningeal coverings of the brain and spinal cord, with significant heritable basis. Genome-wide association studies (GWAS) have previously identified only a single risk locus for meningioma, at 10p12.31.To identify a susceptibility locus for meningioma, we conducted a meta-analysis of 2 GWAS, imputed using a merged reference panel from the 1000 Genomes Project and UK10K data, with validation in 2 independent sample series totaling 2138 cases and 12081 controls.We identified a new susceptibility locus for meningioma at 11p15.5 (rs2686876, odds ratio = 1.44, P = 9.86 × 10-9). A number of genes localize to the region of linkage disequilibrium encompassing rs2686876, including RIC8A, which plays a central role in the development of neural crest-derived structures, such as the meninges.This finding advances our understanding of the genetic basis of meningioma development and provides additional support for a polygenic model of meningioma.

    View details for DOI 10.1093/neuonc/noy077

    View details for Web of Science ID 000448665500008

    View details for PubMedID 29762745

    View details for PubMedCentralID PMC6176799

  • EFFECT OF HEALTH DISPARITIES ON OVERALL SURVIVAL OF PATIENTS WITH GLIOBLASTOMA Mandel, J., Youssef, M., Nam, J., Patel, A., Liu, D., Wu, J., Armstrong, G., Bondy, M., de Groot, J. OXFORD UNIV PRESS INC. 2018: 81
  • Individual, Social, and Societal Correlates of Health-Related Quality of Life Among African American Survivors of Ovarian Cancer: Results from the African American Cancer Epidemiology Study JOURNAL OF WOMENS HEALTH Anderson, R. T., Peres, L. C., Camacho, F., Bandera, E. V., Funkhouser, E., Moorman, P. G., Paddock, L. E., Peters, E. S., Abbott, S. E., Alberg, A. J., Barnholtz-Sloan, J., Bondy, M., Cote, M. L., Schwartz, A. G., Terry, P., Schildkraut, J. M. 2019; 28 (2): 284–93

    Abstract

    While the incidence of epithelial ovarian cancer (EOC) is lower among African American (AA) women compared with European American (EA) women, AA women have markedly worse outcomes. In this study, we describe individual, social, and societal factors in health-related quality of life (HRQL) in AA women diagnosed with EOC in the African American Cancer Epidemiology Study (AACES) that we hypothesize may influence a patient's capacity to psychosocially adjust to a diagnosis of cancer.There were 215 invasive EOC cases included in the analysis. HRQL was measured using the SF-8 component scores for physical (PCS) and mental (MCS) health. We used least squares regression to test the effects of individual dispositional factors (optimism and trait anxiety); social level (perceived social support); and societal-level factors (SES defined as low family income and low educational attainment, and perceived discrimination) on HRQL, while adjusting for patient age, tumor stage, body mass index, and comorbidity. Mediation analysis was applied to test whether social support and physical activity buffer impacts of EOC on HRQL.Optimism, trait anxiety, social support, poverty, and past perceived discrimination were significantly associated with HRQL following diagnosis of EOC. Specifically, higher family income, lower phobic anxiety, and higher social support were associated with better wellbeing on the MCS and PCS (p < 0.01). Higher perceived discrimination was associated with both lower MCS and PCS, whereas higher optimism was associated with higher MCS. Physical activity (MET-min/week) and social support displayed significant overall mediation for effects of SES on MCS and PCS, but not for trait anxiety.Both pre- and postdiagnosis characteristics of AA women with EOC are important predictors of HRQL after cancer diagnosis. Individual, social, and societal-level factors each contribute to HRQL status with EOC and should be assessed.

    View details for DOI 10.1089/jwh.2018.7025

    View details for Web of Science ID 000447015300001

    View details for PubMedID 30307782

  • Impact of acculturation on breast cancer treatment and survivorship care among Mexican American patients in Texas JOURNAL OF CANCER SURVIVORSHIP Advani, P., Bondy, M., Thompson, P. A., Martinez, M., Nodora, J. N., Vernon, S. W., Diamond, P., Burnett, J., Brewster, A. M. 2018; 12 (5): 659–68

    Abstract

    Given the increasing number and diversity of cancer survivors in the USA and persistent racial/ethnic disparities in breast cancer care, we sought to examine the role of acculturation in adherence to recommended surgical treatment and survivorship care recommendations.Study participants included 343 Mexican American women with stage I to III breast cancer who participated in the Ella Binational Breast Cancer Study and were treated at The University of Texas MD Anderson Cancer Center in Houston, Texas, between March 2007 and June 2011. Participants completed a questionnaire measuring acculturation, and clinical and demographic variables were obtained from an institutional database. Multivariable logistic regression models were constructed to examine differences in surgical procedures received and adherence to long-term survivorship care by acculturation level.Bilingual (odds ratio [OR] = 1.85; 95% confidence interval [CI] = 0.85-4.02, P = .11) and English-dominant women (OR = 2.39; 95% CI = 1.02-5.61, P = .04) were more likely to receive breast-conserving surgery (versus mastectomy) than were Spanish-dominant women. Among all patients, adherence to surveillance mammography and clinic visits decreased over time; the decline in clinic visit adherence was statistically significant (P = .005). Although no statistically significant association was found between acculturation and adherence to long-term survivorship care, receipt of breast-conserving surgery (versus mastectomy) was significantly associated with higher adherence to surveillance mammograms.Acculturation may play a role in decision-making about surgical management of breast cancer, and further studies with larger samples are needed to explore its role in adherence to survivorship care recommendations. Findings from this study may help identify patients requiring additional support while making decisions pertaining to their cancer treatment and survivorship care.

    View details for DOI 10.1007/s11764-018-0703-y

    View details for Web of Science ID 000445241100006

    View details for PubMedID 30043339

    View details for PubMedCentralID PMC6436629

  • Distinct epidemiological profiles associated with inflammatory breast cancer (IBC): A comprehensive analysis of the IBC registry at The University of Texas MD Anderson Cancer Center PLOS ONE Fouad, T. M., Ueno, N. T., Yu, R. K., Ensor, J. E., Alvarez, R. H., Krishnamurthy, S., Lucci, A., Reuben, J. M., Yang, W., Willey, J. S., Valero, V., Bondy, M. L., Cristofinalli, M., Shete, S., Woodward, W. A., El-Zein, R. 2018; 13 (9): e0204372

    Abstract

    To date, studies on inflammatory breast cancer (IBC) lack comprehensive epidemiological data. We analyzed detailed prospectively collected clinical and epidemiological data from the IBC Registry at The University of Texas MD Anderson Cancer Center.Patients with IBC (n = 248) were consecutively diagnosed and prospectively enrolled between November 2006 and April 2013. All patients were newly diagnosed and at least 18 years old. Secondary IBC was excluded. Overall 160 variables were collected and evaluated including sociodemographics, anthropometrics, tobacco and alcohol consumption, reproductive variables, and family history data.Mean age at diagnosis was 51.6 (±11.5 SD) years, and the majority of patients were White (77.8%). A mean BMI ≥ 25 kg/m2, irrespective of menopausal status, was observed in 80.2% of all patients, with 82.6% of African Americans being obese. Approximately 42.2% of patients were ever smokers, and 91% reported ever being pregnant. A history of breastfeeding was reported in 54% of patients, with significant differences between ethnic groups in favor of White women (P<0.0001). Other reproductive factors such as use of birth control pills & hormone replacement therapy were also more frequently associated with White women compare to other ethnic groups (P < 0.05). In the multivariate Cox proportional hazard analysis, African American or Hispanic ethnicity, not having breastfed, higher clinical stage, and TNBC subtype were associated with shorter survival.Our data suggest that IBC is associated with distinct epidemiological profiles. This information could assist in targeting patients with specific preventive strategies based on their modifiable behavioral patterns.

    View details for DOI 10.1371/journal.pone.0204372

    View details for Web of Science ID 000445998100034

    View details for PubMedID 30248155

    View details for PubMedCentralID PMC6152950

  • Evaluating glioma risk associated with extent of European admixture in African-Americans and Latinos Ostrom, Q. T., Egan, K. M., Nabors, L., Gerke, T., Thompson, R. C., Olson, J. J., LaRocca, R., Chowdhary, S., Eckel-Passow, J. E., Armstrong, G., Wiencke, J. K., Amos, C. I., Bernstein, J. L., Claus, E. B., Il'yasova, D., Johansen, C., Lachance, D. H., Lai, R., Merrell, R. T., Olson, S. H., Sadetzki, S., Schildkraut, J., Shete, S., Houlston, R. S., Jenkins, R. B., Melin, B., Bondy, M. L., Barnholtz-Sloan, J. S. AMER ASSOC CANCER RESEARCH. 2018
  • Elucidating the molecular pathogenesis of familial glioma Jacobs, D. I., Fukumura, K., Bainbridge, M. N., Armstrong, G. N., Muzny, D. M., Melin, B., Huse, J. T., Bondy, M. L. AMER ASSOC CANCER RESEARCH. 2018
  • Association of genetic variants with fatigue in patients with malignant glioma NEURO-ONCOLOGY PRACTICE Armstrong, T. S., Vera, E., Zhou, R., Acquaye, A. A., Sullaway, C. M., Berger, A. M., Breton, G., Mahajan, A., Wefel, J. S., Gilbert, M. R., Bondy, M., Scheurer, M. E. 2018; 5 (2): 122–28

    Abstract

    Fatigue is a consistently reported, severe symptom among patients with gliomas throughout the disease trajectory. Genomic pathways associated with fatigue in glioma patients have yet to be identified.Clinical factors (performance status, tumor details, age, gender) were collected by chart review on glioma patients with fatigue ("I have lack of energy" on Functional Assessment of Cancer Therapy-Brain), as well as available genotyping data. Candidate genes in clock and inflammatory pathways were identified from a literature review, of which 50 single nucleotide polymorphisms (SNPs) in 7 genes were available. Clinical factors and SNPs identified by univariate analyses were included in a multivariate model for moderate-severe fatigue.The study included 176 patients (median age = 47 years, 67% males). Moderate-severe fatigue was reported by 43%. Results from multivariate analysis revealed poor performance status and 2 SNPs were associated with fatigue severity. Moderate-severe fatigue was more common in patients with poor performance status (OR = 3.52, P < .01). For each additional copy of the minor allele in rs934945 (PER2) the odds of fatigue decreased (OR = 0.51, P < .05). For each additional copy of the minor allele in rs922270 (ARTNL2) the odds of fatigue increased (OR = 2.38, P < .01). Both of these genes are important in the circadian clock pathway, which has been implicated in diurnal preference, and duration and quality of sleep. No genes in the inflammatory pathway were associated with fatigue in the current study.Identifying patients at highest risk for fatigue during treatment allows for improved clinical monitoring and enrichment of patient selection for clinical trials.

    View details for DOI 10.1093/nop/npx020

    View details for Web of Science ID 000432282600008

    View details for PubMedID 31386001

    View details for PubMedCentralID PMC6655500

  • Glioma-related seizures in relation to histopathological subtypes: a report from the glioma international case-control study JOURNAL OF NEUROLOGY Berntsson, S. G., Merrell, R. T., Amirian, E., Armstrong, G. N., Lachance, D., Smits, A., Zhou, R., Jacobs, D. I., Wrensch, M. R., Olson, S. H., Il'yasova, D., Claus, E. B., Barnholtz-Sloan, J. S., Schildkraut, J., Sadetzki, S., Johansen, C., Houlston, R. S., Jenkins, R. B., Bernstein, J. L., Lai, R., Shete, S., Amos, C. I., Bondy, M. L., Melin, B. S. 2018; 265 (6): 1432–42

    Abstract

    The purpose of this study was to evaluate the distribution of glioma-related seizures and seizure control at the time of tumor diagnosis with respect to tumor histologic subtypes, tumor treatment and patient characteristics, and to compare seizure history preceding tumor diagnosis (or study enrollment) between glioma patients and healthy controls.The Glioma International Case Control study (GICC) risk factor questionnaire collected information on demographics, past medical/medication history, and occupational history. Cases from eight centers were also asked detailed questions on seizures in relation to glioma diagnosis; cases (n = 4533) and controls (n = 4171) were also asked about seizures less than 2 years from diagnosis and previous seizure history more than 2 years prior to tumor diagnosis, including childhood seizures.Low-grade gliomas (LGGs), particularly oligodendrogliomas/oligoastrocytomas, had the highest proportion of glioma-related seizures. Patients with low-grade astrocytoma demonstrated the most medically refractory seizures. A total of 83% of patients were using only one antiepileptic drug (AED), which was levetiracetam in 71% of cases. Gross total resection was strongly associated with reduced seizure frequency (p < 0.009). No significant difference was found between glioma cases and controls in terms of seizure occurring more than 2 years before diagnosis or during childhood.Our study showed that glioma-related seizures were most common in low-grade gliomas. Gross total resection was associated with lower seizure frequency. Additionally, having a history of childhood seizures is not a risk factor ***for developing glioma-related seizures or glioma.

    View details for DOI 10.1007/s00415-018-8857-0

    View details for Web of Science ID 000434462300023

    View details for PubMedID 29687214

    View details for PubMedCentralID PMC5990563

  • Molecular subtyping of tumors from patients with familial glioma NEURO-ONCOLOGY Ruiz, V. Y., Praska, C. E., Armstrong, G., Kollmeyer, T. M., Yamada, S., Decker, P. A., Kosel, M. L., Eckel-Passow, J. E., Lachance, D. H., Bainbridge, M. N., Melin, B. S., Bondy, M. L., Jenkins, R. B., Gliogene Consortium 2018; 20 (6): 810–17

    Abstract

    Single-gene mutation syndromes account for some familial glioma (FG); however, they make up only a small fraction of glioma families. Gliomas can be classified into 3 major molecular subtypes based on isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion. We hypothesized that the prevalence of molecular subtypes might differ in familial versus sporadic gliomas and that tumors in the same family should have the same molecular subtype.Participants in the FG study (Gliogene) provided samples for germline DNA analysis. Formalin-fixed, paraffin-embedded tumors were obtained from a subset of FG cases, and DNA was extracted. We analyzed tissue from 75 families, including 10 families containing a second affected family member. Copy number variation data were obtained using a first-generation Affymetrix molecular inversion probe (MIP) array.Samples from 62 of 75 (83%) FG cases could be classified into the 3 subtypes. The prevalence of the molecular subtypes was: 30 (48%) IDH-wildtype, 21 (34%) IDH-mutant non-codeleted, and 11 (19%) IDH-mutant and 1p/19q codeleted. This distribution of molecular subtypes was not statistically different from that of sporadic gliomas (P = 0.54). Of 10 paired FG samples, molecular subtypes were concordant for 7 (κ = 0.59): 3 IDH-mutant non-codeleted, 2 IDH-wildtype, and 2 IDH-mutant and 1p/19q codeleted gliomas.Our data suggest that within individual families, patients develop gliomas of the same molecular subtype. However, we did not observe differences in the prevalence of the molecular subtypes in FG compared with sporadic gliomas. These observations provide further insight into the distribution of molecular subtypes in FG.

    View details for DOI 10.1093/neuonc/nox192

    View details for Web of Science ID 000432685600010

    View details for PubMedID 29040662

    View details for PubMedCentralID PMC5961123

  • Maternal folate genes and aberrant DNA hypermethylation in pediatric acute lymphoblastic leukemia PLOS ONE Schraw, J. M., Yiu, T. T., Lupo, P. J., Tsavachidis, S., Rau, R., Bondy, M. L., Rabin, K. R., Shen, L., Scheurer, M. E. 2018; 13 (5): e0197408

    Abstract

    There is evidence that maternal genotypes in folate-related genes are associated with pediatric acute lymphoblastic leukemia (ALL) independent of offspring genotype. We evaluated the relationship between maternal genotypes in methionine synthase (MTR) and DNA methylation status in ALL to better characterize the molecular mechanism underlying this association.We obtained bone marrow samples from 51 patients with ALL at diagnosis and from 6 healthy donors. Mothers of patients provided a saliva sample and were genotyped at 11 tagSNPs in MTR. DNA methylation was measured in bone marrow mononuclear cells of patients and six healthy marrow donors. We used hierarchical clustering to identify patients with a hypermethylator phenotype based on 281 differentially methylated promoter CpGs. We used logistic regression to estimate the effects of maternal genotype on the likelihood of DNA hypermethylation in ALL and Ingenuity Pathway Analysis to identify networks enriched for differentially methylated genes.Twenty-two cases (43%) demonstrated promoter hypermethylation, which was more frequent among those with ETV6-RUNX1 fusion and initial white blood cell count < 50 x 109/L. Maternal rs12759827 was associated with aberrant DNA methylation (odds ratio [OR] 4.67, 95% confidence interval 1.46-16.31); non-significantly elevated ORs were observed for all other SNPs. Aberrantly methylated promoter CpGs aligned to genes with known cancer-related functions.Maternal folate metabolic genotype may be associated with DNA methylation patterns in ALL in their offspring. Therefore, the effect of maternal genotypes on ALL susceptibility may act through aberrant promoter methylation, which may contribute to the in utero origins of ALL.

    View details for DOI 10.1371/journal.pone.0197408

    View details for Web of Science ID 000432118800048

    View details for PubMedID 29763473

    View details for PubMedCentralID PMC5953491

  • Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21 SCIENTIFIC REPORTS Ostrom, Q. T., Kinnersley, B., Wrensch, M. R., Eckel-Passow, J. E., Armstrong, G., Rice, T., Chen, Y., Wiencke, J. K., McCoy, L. S., Hansen, H. M., Amos, C. I., Bernstein, J. L., Claus, E. B., Il'yasova, D., Johansen, C., Lachance, D. H., Lai, R. K., Merrell, R. T., Olson, S. H., Sadetzki, S., Schildkraut, J. M., Shete, S., Rubin, J. B., Lathia, J. D., Berens, M. E., Andersson, U., Rajaraman, P., Chanock, S. J., Linet, M. S., Wang, Z., Yeager, M., Houlston, R. S., Jenkins, R. B., Melin, B., Bondy, M. L., Barnholtz-Sloan, J. S., GliomaScan Consortium 2018; 8: 7352

    Abstract

    Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.

    View details for DOI 10.1038/s41598-018-24580-z

    View details for Web of Science ID 000431737300038

    View details for PubMedID 29743610

    View details for PubMedCentralID PMC5943590

  • Genome-Wide Association Studies in Glioma CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Kinnersley, B., Houlston, R. S., Bondy, M. L. 2018; 27 (4): 418–28

    Abstract

    Since the first reports in 2009, genome-wide association studies (GWAS) have been successful in identifying germline variants associated with glioma susceptibility. In this review, we describe a chronological history of glioma GWAS, culminating in the most recent study comprising 12,496 cases and 18,190 controls. We additionally summarize associations at the 27 glioma-risk SNPs that have been reported so far. Future efforts are likely to be principally focused on assessing association of germline-risk SNPs with particular molecular subgroups of glioma, as well as investigating the functional basis of the risk loci in tumor formation. These ongoing studies will be important to maximize the impact of research into glioma susceptibility, both in terms of insight into tumor etiology as well as opportunities for clinical translation. Cancer Epidemiol Biomarkers Prev; 27(4); 418-28. ©2018 AACRSee all articles in this CEBP Focus section, "Genome-Wide Association Studies in Cancer."

    View details for DOI 10.1158/1055-9965.EPI-17-1080

    View details for Web of Science ID 000429048400006

    View details for PubMedID 29382702

    View details for PubMedCentralID PMC5931394

  • Racial/ethnic differences in the epidemiology of ovarian cancer: a pooled analysis of 12 case-control studies INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Peres, L. C., Risch, H., Terry, K. L., Webb, P. M., Goodman, M. T., Wu, A. H., Alberg, A. J., Bandera, E. V., Barnholtz-Sloan, J., Bondy, M. L., Cote, M. L., Funkhouser, E., Moorman, P. G., Peters, E. S., Schwartz, A. G., Terry, P. D., Manichaikul, A., Abbott, S. E., Camacho, F., Jordan, S. J., Nagle, C. M., Rossing, M., Doherty, J. A., Modugno, F., Moysich, K., Ness, R., Berchuck, A., Cook, L., Nhu Le, Brooks-Wilson, A., Sieh, W., Whittemore, A., McGuire, V., Rothstein, J., Anton-Culver, H., Ziogas, A., Pearce, C. L., Tseng, C., Pike, M., Schildkraut, J. M., Australian Ovarian Canc Study Grp, African Amer Canc Epidemiology Stu, Ovarian Canc Assoc Consortium 2018; 47 (2): 460–72

    Abstract

    Ovarian cancer incidence differs substantially by race/ethnicity, but the reasons for this are not well understood. Data were pooled from the African American Cancer Epidemiology Study (AACES) and 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC) to examine racial/ethnic differences in epidemiological characteristics with suspected involvement in epithelial ovarian cancer (EOC) aetiology.We used multivariable logistic regression to estimate associations for 17 reproductive, hormonal and lifestyle characteristics and EOC risk by race/ethnicity among 10 924 women with invasive EOC (8918 Non-Hispanic Whites, 433 Hispanics, 911 Blacks, 662 Asian/Pacific Islanders) and 16 150 controls (13 619 Non-Hispanic Whites, 533 Hispanics, 1233 Blacks, 765 Asian/Pacific Islanders). Likelihood ratio tests were used to evaluate heterogeneity in the risk factor associations by race/ethnicity.We observed statistically significant racial/ethnic heterogeneity for hysterectomy and EOC risk (P = 0.008), where the largest odds ratio (OR) was observed in Black women [OR = 1.64, 95% confidence interval (CI) = 1.34-2.02] compared with other racial/ethnic groups. Although not statistically significant, the associations for parity, first-degree family history of ovarian or breast cancer, and endometriosis varied by race/ethnicity. Asian/Pacific Islanders had the greatest magnitude of association for parity (≥3 births: OR = 0.38, 95% CI = 0.28-0.54), and Black women had the largest ORs for family history (OR = 1.77, 95% CI = 1.42-2.21) and endometriosis (OR = 2.42, 95% CI = 1.65-3.55).Although racial/ethnic heterogeneity was observed for hysterectomy, our findings support the validity of EOC risk factors across all racial/ethnic groups, and further suggest that any racial/ethnic population with a higher prevalence of a modifiable risk factor should be targeted to disseminate information about prevention.

    View details for PubMedID 29211900

    View details for PubMedCentralID PMC5913601

  • Mendelian randomisation study of the relationship between vitamin D and risk of glioma SCIENTIFIC REPORTS Takahashi, H., Cornish, A. J., Sud, A., Law, P. J., Kinnersley, B., Ostrom, Q. T., Labreche, K., Eckel-Passow, J. E., Armstrong, G. N., Claus, E. B., Il'yasova, D., Schildkraut, J., Barnholtz-Sloan, J. S., Olson, S. H., Bernstein, J. L., Lai, R. K., Schoemaker, M. J., Simon, M., Hoffmann, P., Noethen, M. M., Joeckel, K., Chanock, S., Rajaraman, P., Johansen, C., Jenkins, R. B., Melin, B. S., Wrensch, M. R., Sanson, M., Bondy, M. L., Turnbull, C., Houlston, R. S. 2018; 8: 2339

    Abstract

    To examine for a causal relationship between vitamin D and glioma risk we performed an analysis of genetic variants associated with serum 25-hydroxyvitamin D (25(OH)D) levels using Mendelian randomisation (MR), an approach unaffected by biases from confounding. Two-sample MR was undertaken using genome-wide association study data. Single nucleotide polymorphisms (SNPs) associated with 25(OH)D levels were used as instrumental variables (IVs). We calculated MR estimates for the odds ratio (OR) for 25(OH)D levels with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighted (IVW) and maximum likelihood estimation (MLE) methods. A non-significant association between 25(OH)D levels and glioma risk was shown using both the IVW (OR = 1.21, 95% confidence interval [CI] = 0.90-1.62, P = 0.201) and MLE (OR = 1.20, 95% CI = 0.98-1.48, P = 0.083) methods. In an exploratory analysis of tumour subtype, an inverse relationship between 25(OH)D levels and glioblastoma (GBM) risk was identified using the MLE method (OR = 0.62, 95% CI = 0.43-0.89, P = 0.010), but not the IVW method (OR = 0.62, 95% CI = 0.37-1.04, P = 0.070). No statistically significant association was shown between 25(OH)D levels and non-GBM glioma. Our results do not provide evidence for a causal relationship between 25(OH)D levels and all forms of glioma risk. More evidence is required to explore the relationship between 25(OH)D levels and risk of GBM.

    View details for DOI 10.1038/s41598-018-20844-w

    View details for Web of Science ID 000424087700011

    View details for PubMedID 29402980

    View details for PubMedCentralID PMC5799201

  • Combined Proteomic-Molecular Epidemiology Approach to Identify Precision Targets in Brain Cancer ACS CHEMICAL NEUROSCIENCE Mostovenko, E., Lu, Y., Amirian, E., Tsavachidis, S., Armstrong, G. N., Bondy, M. L., Nilsson, C. L. 2018; 9 (1): 80–84

    Abstract

    Primary brain tumors are predominantly malignant gliomas. Grade IV astrocytomas (glioblastomas, GBM) are among the most deadly of all tumors; most patients will succumb to their disease within 2 years of diagnosis despite standard of care. The grim outlook for brain tumor patients indicates that novel precision therapeutic targets must be identified. Our hypothesis is that the cancer proteomes of glioma tumors may contain protein variants that are linked to the aggressive pathology of the disease. To this end, we devised a novel workflow that combined variant proteomics with molecular epidemiological mining of public cancer data sets to identify 10 previously unrecognized variants linked to the risk of death in low grade glioma or GBM. We hypothesize that a subset of the protein variants may be successfully developed in the future as novel targets for malignant gliomas.

    View details for DOI 10.1021/acschemneuro.7b00165

    View details for Web of Science ID 000423016300009

    View details for PubMedID 28657708

    View details for PubMedCentralID PMC5764832

  • Quality of life after surgery for intracranial meningioma CANCER Benz, L. S., Wrensch, M. R., Schildkraut, J. M., Bondy, M. L., Warren, J. L., Wiemels, J. L., Claus, E. B. 2018; 124 (1): 161–66

    Abstract

    To the authors' knowledge, limited data exist regarding long-term quality of life (QOL) for patients diagnosed with intracranial meningioma.The data in the current study concerned 1722 meningioma cases diagnosed among residents of Connecticut, Massachusetts, California, Texas, and North Carolina from May 1, 2006 through March 14, 2013, and 1622 controls who were frequency matched to the cases by age, sex, and geography. These individuals were participants in a large, population-based, case-control study. Telephone interviews were used to collect data regarding QOL at the time of initial diagnosis or contact, using the Medical Outcomes Study Short-Form 36 Health Survey. QOL outcomes were compared by case/control status.Patients diagnosed with meningioma reported levels of physical, emotional, and mental health functioning below those reported in a general healthy population. Case participants and controls differed most significantly with regard to the domains of Physical and Social Functioning, Role-Physical, Role-Emotional, and Vitality.In the current study, patients with meningioma experienced statistically significant decreases in QOL compared with healthy controls of a similar demographic breakdown, although these differences were found to vary in clinical significance. Cancer 2018;124:161-6. © 2017 American Cancer Society.

    View details for DOI 10.1002/cncr.30975

    View details for Web of Science ID 000418251600020

    View details for PubMedID 28902404

    View details for PubMedCentralID PMC6415762

  • Germline polymorphisms in myeloid-associated genes are not associated with survival in glioma patients JOURNAL OF NEURO-ONCOLOGY Jacobs, D. I., Liu, Y., Gabrusiewicz, K., Tsavachidis, S., Armstrong, G. N., Zhou, R., Wei, J., Ivan, C., Calin, G., Molinaro, A. M., Rice, T., Bracci, P. M., Hansen, H. M., Wiencke, J. K., Wrensch, M. R., Heimberger, A. B., Bondy, M. L. 2018; 136 (1): 33–39

    Abstract

    Immune cells of myeloid origin, including microglia, macrophages, and myeloid-derived suppressor cells adopt immunosuppressive phenotypes that support gliomagenesis. Here, we tested an a priori hypothesis that single nucleotide polymorphisms (SNPs) in genes related to glioma-associated myeloid cell regulation and function are also associated with patient survival after glioma diagnosis. Subjects for this study were 992 glioma patients treated at The University of Texas MD Anderson Cancer Center in Houston, Texas between 1992 and 2008. Haplotype-tagging SNPs in 91 myeloid-associated genes were analyzed for association with survival by Cox regression. Individual SNP- and gene-based tests were performed separately in glioblastoma (WHO grade IV, n = 511) and lower-grade glioma (WHO grade II-III, n = 481) groups. After adjustment for multiple testing, no myeloid-associated gene variants were significantly associated with survival in glioblastoma. Two SNPs, rs147960238 in CD163 (p = 2.2 × 10-5) and rs17138945 in MET (p = 5.6 × 10-5) were significantly associated with survival of patients with lower-grade glioma. However, these associations were not confirmed in an independent analysis of 563 lower-grade glioma cases from the University of California at San Francisco Adult Glioma Study (p = 0.65 and p = 0.41, respectively). The results of this study do not support a role for inherited polymorphisms in myeloid-associated genes in affecting survival of patients diagnosed with glioblastoma or lower-grade glioma.

    View details for DOI 10.1007/s11060-017-2622-6

    View details for Web of Science ID 000419472500004

    View details for PubMedID 28965162

    View details for PubMedCentralID PMC5756111

  • SEX-SPECIFIC GENE AND PATHWAY MODELING OF INHERITED GLIOMA RISK Ostrom, Q., Rubin, J., Lathia, J., Berens, M., Speyer, G., Coleman, W., Huang, W., Liao, P., Amos, C., Armstrong, G., Bernstein, J., Claus, E., Eckel-Passow, J., Hansen, H., Houlston, R., Il'yasova, D., Jenkins, R., Johansen, C., Lachance, D., Lai, R., Lau, C., McCoy, L., Merrell, R., Olson, S., Rice, T., Sadetzki, S., Schildkraut, J., Shete, S., Wiencke, J., Melin, B., Wrensch, M., Bondy, M., Barnholtz-Sloan, J. OXFORD UNIV PRESS INC. 2017: 104
  • EVALUATING GLIOMA RISK ASSOCIATED WITH EXTENT OF EUROPEAN ADMIXTURE IN AFRICAN-AMERICANS AND LATINOS Ostrom, Q., Egan, K., Nabors, B., Amos, C., Armstrong, G., Bernstein, J., Chowdhary, S., Claus, E., Eckel-Passow, J., Gerke, T., Houlston, R., Il'yasova, D., Jenkins, R., Johansen, C., Lachance, D., Lai, R., LaRocca, R., Lau, C., Merrell, R., Olson, J. J., Olson, S., Sadetzki, S., Schildkraut, J., Shete, S., Thompson, R., Wrensch, M., Wiencke, J., Melin, B., Bondy, M., Barnholtz-Sloan, J. OXFORD UNIV PRESS INC. 2017: 102–3
  • Dietary Quality and Ovarian Cancer Risk in African-American Women AMERICAN JOURNAL OF EPIDEMIOLOGY Qin, B., Moorman, P. G., Kelemen, L. E., Alberg, A. J., Barnholtz-Sloan, J. S., Bondy, M., Cote, M. L., Funkhouser, E., Peters, E. S., Schwartz, A. G., Terry, P., Schildkraut, J. M., Bandera, E. V. 2017; 185 (12): 1281–89

    Abstract

    This study evaluated 3 index-based dietary patterns-Healthy Eating Index (HEI)-2005, HEI-2010, and Alternate Healthy Eating Index (AHEI)-2010-in relation to ovarian cancer risk in African-American women. The study was conducted among 415 ovarian cancer cases and 629 age- and site-matched controls of African-American descent recruited from the population-based African American Cancer Epidemiology Study. Multivariable unconditional logistic regression models were used to estimate odds ratios and 95% confidence intervals between quartiles of dietary quality indices and ovarian cancer risk, adjusting for potential confounders. We found that higher AHEI-2010 scores, but not HEI-2005 or HEI-2010 scores, were associated with lower risk of ovarian cancer (comparing the highest quartile (4th) vs. lowest (1st), odds ratio (OR) = 0.66, 95% confidence interval (CI): 0.45, 0.98; P for trend = 0.05). When stratified by menopausal status, no noteworthy associations were observed among premenopausal women. However, among postmenopausal women, greater adherence to HEI-2010 (quartile 4 vs. quartile 1, OR = 0.57, 95% CI: 0.36, 0.92; P for trend = 0.03) and AHEI-2010 (quartile 4 vs. quartile 1, OR = 0.49, 95% CI: 0.31, 0.78; P for trend = 0.01) were inversely associated with ovarian cancer. Our findings indicate that adherence to an overall healthy dietary pattern may reduce ovarian cancer risk in African-American women, and particularly among postmenopausal African-American women.

    View details for DOI 10.1093/aje/kwx022

    View details for Web of Science ID 000404383400010

    View details for PubMedID 28535290

    View details for PubMedCentralID PMC5860470

  • Cytoplasmic Cyclin E Predicts Recurrence in Patients with Breast Cancer CLINICAL CANCER RESEARCH Hunt, K. K., Karakas, C., Ha, M., Biernacka, A., Yi, M., Sahin, A. A., Adjapong, O., Hortobagyi, G. N., Bondy, M. L., Thompson, P. A., Cheung, K., Ellis, I. O., Bacus, S., Symmans, W., Kim-Anh Do, Keyomarsi, K. 2017; 23 (12): 2991–3002

    Abstract

    Purpose: Low molecular weight cyclin E (LMW-E) detected by Western blot analysis predicts for reduced breast cancer survival; however, it is impractical for clinical use. LMW-E lacks a nuclear localization signal that leads to accumulation in the cytoplasm that can be detected by IHC. We tested the hypothesis that cytoplasmic staining of cyclin E can be used as a predictor of poor outcome in different subtypes of breast cancer using patient cohorts with distinct clinical and pathologic features.Experimental Design: We evaluated the subcellular localization of cyclin E in breast cancer specimens from 2,494 patients from 4 different cohorts: 303 from a prospective study and 2,191 from retrospective cohorts [NCI, MD Anderson Cancer Center (MDA), and the United Kingdom (UK)]. Median follow-up times were 8.0, 10.1, 13.5, and 5.7 years, respectively.Results: Subcellular localization of cyclin E on IHC was associated with full-length (nuclear) and low molecular weight isoforms (cytoplasmic) of cyclin E on Western blot analysis. In multivariable analysis, cytoplasmic cyclin E staining was associated with the greatest risk of recurrence compared with other prognostic factors across all subtypes in three (NCI, MDA, and UK) of the cohorts. In the MDA cohort, cytoplasmic cyclin E staining outperformed Ki67 and all other variables as prognostic factors.Conclusions: Cytoplasmic cyclin E identifies patients with the highest likelihood of recurrence consistently across different patient cohorts and subtypes. These patients may benefit from alternative therapies targeting the oncogenic isoforms of cyclin E. Clin Cancer Res; 23(12); 2991-3002. ©2016 AACR.

    View details for DOI 10.1158/1078-0432.CCR-16-2217

    View details for Web of Science ID 000403330000016

    View details for PubMedID 27881578

    View details for PubMedCentralID PMC5441976

  • Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors NATURE GENETICS Melin, B. S., Barnholtz-Sloan, J. S., Wrensch, M. R., Johansen, C., Il'yasova, D., Kinnersley, B., Ostrom, Q. T., Labreche, K., Chen, Y., Armstrong, G., Liu, Y., Eckel-Passow, J. E., Decker, P. A., Labussiere, M., Idbaih, A., Hoang-Xuan, K., Di Stefano, A., Mokhtari, K., Delattre, J., Broderick, P., Galan, P., Gousias, K., Schramm, J., Schoemaker, M. J., Fleming, S. J., Herms, S., Heilmann, S., Noethen, M. M., Wichmann, H., Schreiber, S., Swerdlow, A., Lathrop, M., Simon, M., Sanson, M., Andersson, U., Rajaraman, P., Chanock, S., Linet, M., Wang, Z., Yeager, M., Wiencke, J. K., Hansen, H., Mccoy, L., Rice, T., Kosel, M. L., Sicotte, H., Amos, C. I., Bernstein, J. L., Davis, F., Lachance, D., Lau, C., Merrell, R. T., Shildkraut, J., Ali-Osman, F., Sadetzki, S., Scheurer, M., Shete, S., Lai, R. K., Claus, E. B., Olson, S. H., Jenkins, R. B., Houlston, R. S., Bondy, M. L., GliomaScan Consortium 2017; 49 (5): 789-+

    Abstract

    Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 × 10-9, odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 × 10-10, OR = 1.24), 16p13.3 (rs2562152; P = 1.93 × 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 × 10-11, OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 × 10-10, OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 × 10-9, OR = 1.19), 1q44 (rs12076373; P = 2.63 × 10-10, OR = 1.23), 2q33.3 (rs7572263; P = 2.18 × 10-10, OR = 1.20), 3p14.1 (rs11706832; P = 7.66 × 10-9, OR = 1.15), 10q24.33 (rs11598018; P = 3.39 × 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 × 10-10, OR = 1.16), 14q12 (rs10131032; P = 5.07 × 10-11, OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 × 10-9, OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.

    View details for DOI 10.1038/ng.3823

    View details for Web of Science ID 000400051400019

    View details for PubMedID 28346443

    View details for PubMedCentralID PMC5558246

  • The History of a Name: The American Society for Preventive Oncology Renames Its Highest Honor the Joseph F. Fraumeni, Jr., Distinguished Achievement Award CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Newcomb, P. A., Hsing, A. B., Bondy, M. L., Neugut, A. I. 2017; 26 (3): 431-432
  • Cyclin E overexpression as a biomarker for combination treatment strategies in inflammatory breast cancer ONCOTARGET Alexander, A., Karakas, C., Chen, X., Carey, J. W., Yi, M., Bondy, M., Thompson, P., Cheung, K., Ellis, I. O., Gong, Y., Krishnamurthy, S., Alvarez, R. H., Ueno, N. T., Hunt, K. K., Keyomarsi, K. 2017; 8 (9): 14897–911

    Abstract

    Inflammatory breast cancer (IBC) is a virulent form of breast cancer, and novel treatment strategies are urgently needed. Immunohistochemical analysis of tumors from women with a clinical diagnosis of IBC (n = 147) and those with non-IBC breast cancer (n = 2510) revealed that, whereas in non-IBC cases cytoplasmic cyclin E was highly correlated with poor prognosis (P < 0.001), in IBC cases both nuclear and cytoplasmic cyclin E were indicative of poor prognosis. These results underscored the utility of the cyclin E/CDK2 complex as a novel target for treatment. Because IBC cell lines were highly sensitive to the CDK2 inhibitors dinaciclib and meriolin 5, we developed a high-throughput survival assay (HTSA) to design novel sequential combination strategies based on the presence of cyclin E and CDK2. Using a 14-cell-line panel, we found that dinaciclib potentiated the activity of DNA-damaging chemotherapies treated in a sequence of dinaciclib followed by chemotherapy, whereas this was not true for paclitaxel. We also identified a signature of DNA repair-related genes that are downregulated by dinaciclib, suggesting that global DNA repair is inhibited and that prolonged DNA damage leads to apoptosis. Taken together, our findings argue that CDK2-targeted combinations may be viable strategies in IBC worthy of future clinical investigation.

    View details for DOI 10.18632/oncotarget.14689

    View details for Web of Science ID 000396013700056

    View details for PubMedID 28107181

    View details for PubMedCentralID PMC5362453

  • Analyzing semi-competing risks data with missing cause of informative terminal event STATISTICS IN MEDICINE Zhou, R., Zhu, H., Bondy, M., Ning, J. 2017; 36 (5): 738–53

    Abstract

    Cancer studies frequently yield multiple event times that correspond to landmarks in disease progression, including non-terminal events (i.e., cancer recurrence) and an informative terminal event (i.e., cancer-related death). Hence, we often observe semi-competing risks data. Work on such data has focused on scenarios in which the cause of the terminal event is known. However, in some circumstances, the information on cause for patients who experience the terminal event is missing; consequently, we are not able to differentiate an informative terminal event from a non-informative terminal event. In this article, we propose a method to handle missing data regarding the cause of an informative terminal event when analyzing the semi-competing risks data. We first consider the nonparametric estimation of the survival function for the terminal event time given missing cause-of-failure data via the expectation-maximization algorithm. We then develop an estimation method for semi-competing risks data with missing cause of the terminal event, under a pre-specified semiparametric copula model. We conduct simulation studies to investigate the performance of the proposed method. We illustrate our methodology using data from a study of early-stage breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.

    View details for DOI 10.1002/sim.7161

    View details for Web of Science ID 000393303200002

    View details for PubMedID 27813148

    View details for PubMedCentralID PMC5241235

  • POLYMORPHISMS IN MYELOID-ASSOCIATED GENES PREDICT GLIOMA SURVIVAL Heimberger, A., Liu, Y., Gabrusiewicz, K., Amirian, E., Tsavachidis, S., Armstrong, G., Zhou, R., Wei, J., Ivan, C., Calin, G., Scheurer, M., Dahlin, A., Melin, B., Bondy, M. OXFORD UNIV PRESS INC. 2016: 58
  • OCCURRENCE AND IMPLICATIONS OF MYELOSUPPRESSION DURING CONCURRENT THERAPY ON RTOG 0825 Vera, E., Scheurer, M., Zhou, R., Gilbert, M. R., Bondy, M., Sulman, E., Yuan, Y., Liu, Y., Wendland, M., Brachman, D., Bearden, J., McGovern, S. L., Wilson, S., Judy, K., Robins, H., Hunter, G., Crocker, I. R., Chao, S., Kaluza, V., Pugh, S., Armstrong, T. S. OXFORD UNIV PRESS INC. 2016: 6
  • DEMOGRAPHICS AND LIFESTYLE FACTORS IN GLIOMA RISK: A REPORT FROM THE GLIOMA INTERNATIONAL CASE-CONTROL STUDY Amirian, E., Armstrong, G., Zhou, R., Wrensch, M., Olson, S., Scheurer, M., Il'yasova, D., Lachance, D., Lau, C., Claus, E., Barnholtz-Sloan, J., Schildkraut, J., Ali-Osman, F., Sadetzki, S., Johansen, C., Houlston, R., Jenkins, R., Bernstein, J., Merrell, R., Davis, F., Lai, R., Shete, S., Amos, C., Melin, B., Bondy, M. OXFORD UNIV PRESS INC. 2016: 57–58
  • Association between Body Powder Use and Ovarian Cancer: The African American Cancer Epidemiology Study (AACES) CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Schildkraut, J. M., Abbott, S. E., Alberg, A. J., Bandera, E. V., Barnholtz-Sloan, J. S., Bondy, M. L., Cote, M. L., Funkhouser, E., Peres, L. C., Peters, E. S., Schwartz, A. G., Terry, P., Crankshaw, S., Camacho, F., Wang, F., Moorman, P. G. 2016; 25 (10): 1411–17

    Abstract

    Epidemiologic studies indicate increased ovarian cancer risk among women who use genital powder, but this has not been thoroughly investigated in African American (AA) women, a group with a high prevalence of use. We evaluate the relationship between use of genital powder and nongenital powder in invasive epithelial ovarian cancer (EOC).Subjects are 584 cases and 745 controls enrolled in the African American Cancer Epidemiology Study (AACES), an ongoing, population-based case-control study of EOC in AA women in 11 geographic locations in the United States. AA controls were frequency matched to cases on residence and age. Logistic regression was used to calculate ORs and 95% confidence intervals (CI) for associations between genital and nongenital powder exposure and EOC risk, controlling for potential confounders.Powder use was common (62.8% of cases and 52.9% of controls). Genital powder was associated with an increased risk of EOC (OR = 1.44; 95% CI, 1.11-1.86) and a dose-response relationship was found for duration of use and number of lifetime applications (P < 0.05). Nongenital use was also associated with EOC risk, particularly among nonserous EOC cases (OR = 2.28; 95% CI, 1.39-3.74). An association between powder use and upper respiratory conditions suggests an enhanced inflammatory response may explain the association between body powder and EOC.In a study of AA women, body powder use was significantly associated with EOC risk.The results support that body powder is a modifiable risk factor for EOC among AA women. Cancer Epidemiol Biomarkers Prev; 25(10); 1411-7. ©2016 AACRSee related commentary by Trabert, p. 1369.

    View details for DOI 10.1158/1055-9965.EPI-15-1281

    View details for Web of Science ID 000385642800006

    View details for PubMedID 27197282

    View details for PubMedCentralID PMC5050086

  • Mode of Delivery in Premature Neonates: Does It Matter? AJP REPORTS Racusin, D. A., Antony, K. M., Haase, J., Bondy, M., Aagaard, K. M. 2016; 6 (3): E251–E259

    Abstract

    Despite the current prevalence of preterm births, no clear guidelines exist on the optimal mode of delivery. Our objective was to investigate the effects of mode of delivery on neonatal outcomes among premature infants in a large cohort.We applied a retrospective cohort study design to a database of 6,408 births. Neonates were stratified by birth weight and a composite score was calculated to assess neonatal outcomes. The results were then further stratified by fetal exposure to antenatal steroids, birth weight, and mode of delivery.No improvement in neonatal outcome with cesarean delivery (CD) was noted when subjects were stratified by mode of delivery, both in the presence or absence of antenatal corticosteroid administration. In the 1,500 to 1,999 g subgroup, there appears to be an increased risk of respiratory distress syndromes in neonates born by CD.In our all-comers cohort, replicative of everyday obstetric practice, CD did not improve neonatal outcomes in preterm infants.

    View details for DOI 10.1055/s-0036-1585577

    View details for Web of Science ID 000382531200001

    View details for PubMedID 27468363

    View details for PubMedCentralID PMC4958016

  • Semiparametric model for semi-competing risks data with application to breast cancer study LIFETIME DATA ANALYSIS Zhou, R., Zhu, H., Bondy, M., Ning, J. 2016; 22 (3): 456–71

    Abstract

    For many forms of cancer, patients will receive the initial regimen of treatments, then experience cancer progression and eventually die of the disease. Understanding the disease process in patients with cancer is essential in clinical, epidemiological and translational research. One challenge in analyzing such data is that death dependently censors cancer progression (e.g., recurrence), whereas progression does not censor death. We deal with the informative censoring by first selecting a suitable copula model through an exploratory diagnostic approach and then developing an inference procedure to simultaneously estimate the marginal survival function of cancer relapse and an association parameter in the copula model. We show that the proposed estimators possess consistency and weak convergence. We use simulation studies to evaluate the finite sample performance of the proposed method, and illustrate it through an application to data from a study of early stage breast cancer.

    View details for DOI 10.1007/s10985-015-9344-x

    View details for Web of Science ID 000384534100007

    View details for PubMedID 26340889

    View details for PubMedCentralID PMC4779437

  • Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Childs, E. J., Chaffee, K. G., Gallinger, S., Syngal, S., Schwartz, A. G., Cote, M. L., Bondy, M. L., Hruban, R. H., Chanock, S. J., Hoover, R. N., Fuchs, C. S., Rider, D. N., Amundadottir, L. T., Stolzenberg-Solomon, R., Wolpin, B. M., Risch, H. A., Goggins, M. G., Petersen, G. M., Klein, A. P. 2016; 25 (7): 1185–91

    Abstract

    Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e., BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 early-onset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iSelect Collaborative Oncological Gene-Environment Study (iCOGS) array with custom content. Logistic regression was performed using a log-linear additive model. We replicated several previously reported pancreatic cancer susceptibility loci, including recently identified variants on 2p13.3 and 7p13 (2p13.3, rs1486134: OR = 1.36; 95% CI, 1.13-1.63; P = 9.29 × 10(-4); 7p13, rs17688601: OR = 0.76; 95% CI, 0.63-0.93; P = 6.59 × 10(-3)). For the replicated loci, the magnitude of association observed in these high-risk patients was similar to that observed in studies of unselected patients. In addition to the established pancreatic cancer loci, we also found suggestive evidence of association (P < 5 × 10(-5)) to pancreatic cancer for SNPs at HDAC9 (7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 25(7); 1185-91. ©2016 AACR.

    View details for DOI 10.1158/1055-9965.EPI-15-1217

    View details for Web of Science ID 000380072700022

    View details for PubMedID 27197284

    View details for PubMedCentralID PMC5321211

  • History of chickenpox in glioma risk: a report from the glioma international case-control study (GICC) CANCER MEDICINE Amirian, E., Scheurer, M. E., Zhou, R., Wrensch, M. R., Armstrong, G. N., Lachance, D., Olson, S. H., Lau, C. C., Claus, E. B., Barnholtz-Sloan, J. S., Il'yasova, D., Schildkraut, J., Ali-Osman, F., Sadetzki, S., Jenkins, R. B., Bernstein, J. L., Merrell, R. T., Davis, F. G., Lai, R., Shete, S., Amos, C. I., Melin, B. S., Bondy, M. L. 2016; 5 (6): 1352–58

    Abstract

    Varicella zoster virus (VZV) is a neurotropic α-herpesvirus that causes chickenpox and establishes life-long latency in the cranial nerve and dorsal root ganglia of the host. To date, VZV is the only virus consistently reported to have an inverse association with glioma. The Glioma International Case-Control Study (GICC) is a large, multisite consortium with data on 4533 cases and 4171 controls collected across five countries. Here, we utilized the GICC data to confirm the previously reported associations between history of chickenpox and glioma risk in one of the largest studies to date on this topic. Using two-stage random-effects restricted maximum likelihood modeling, we found that a positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex (95% confidence intervals (CI): 0.65-0.96). Furthermore, the protective effect of chickenpox was stronger for high-grade gliomas. Our study provides additional evidence that the observed protective effect of chickenpox against glioma is unlikely to be coincidental. Future studies, including meta-analyses of the literature and investigations of the potential biological mechanism, are warranted.

    View details for DOI 10.1002/cam4.682

    View details for Web of Science ID 000380048700041

    View details for PubMedID 26972449

    View details for PubMedCentralID PMC4924393

  • The Association Between Body Mass Index and Presenting Symptoms in African American Women with Ovarian Cancer JOURNAL OF WOMENS HEALTH Erondu, C. O., Alberg, A. J., Bandera, E. V., Barnholtz-Sloan, J., Bondy, M., Cote, M. L., Funkhouser, E., Peters, E., Schwartz, A. G., Terry, P. D., Wallace, K., Akushevich, L., Wang, F., Crankshaw, S., Berchuck, A., Schildkraut, J. M., Moorman, P. G. 2016; 25 (6): 571–78

    Abstract

    Ovarian cancer, the most lethal gynecologic malignancy, typically comes to clinical attention due to nonspecific gastrointestinal or pelvic symptoms. African Americans with ovarian cancer have a greater mortality burden than whites and are also much more likely to be obese. The objective of this study is to explore whether the presentation and duration of symptoms differ by body mass index (BMI) in African Americans with ovarian cancer.We conducted a case-only analysis using data from a multicenter population-based study of invasive epithelial ovarian cancer in African American women. Information on risk factors and symptoms leading to diagnosis was obtained in a telephone interview. Frequency and duration of symptoms by BMI categories were compared using logistic regression and linear regression analyses.Of the 326 women, ∼60% was obese (BMI ≥30), with 30.8% having a BMI ≥35 kg/m(2). Ninety-four percent of women reported ≥1 symptom during the year before diagnosis. We observed differences in frequency of symptoms by BMI categories, with most being reported more frequently by the heaviest women. The reported duration of symptoms was longer in women with higher BMI, with statistically significant trend tests for 6 of the 10 symptoms evaluated.BMI appears to impact ovarian cancer symptomatology. Women with higher BMI report having symptoms for a longer period of time before diagnosis of ovarian cancer. Healthcare providers should be vigilant and consider ovarian cancer in the differential diagnosis for obese women presenting with abdominal and pelvic symptoms.

    View details for DOI 10.1089/jwh.2015.5359

    View details for Web of Science ID 000377428900004

    View details for PubMedID 26886855

    View details for PubMedCentralID PMC4900212

  • Recreational physical activity and ovarian cancer risk in African American women CANCER MEDICINE Abbott, S. E., Bandera, E. V., Qin, B., Peres, L. C., Moorman, P. G., Barnholtz-Sloan, J., Schwartz, A. G., Funkhouser, E., Peters, E. S., Cote, M. L., Alberg, A. J., Terry, P., Bondy, M., Paddock, L. E., Crankshaw, S., Wang, F., Camacho, F., Schildkraut, J. M. 2016; 5 (6): 1319–27

    Abstract

    The literature on recreational physical activity (RPA) and ovarian cancer risk is inconclusive and most studies of RPA and ovarian cancer have been conducted in white populations. This study is the first to investigate the association between RPA and ovarian cancer in an exclusively African American (AA) population. We analyzed data from an ongoing U.S. population-based, case-control study of AA women, which included 393 women recently diagnosed with invasive epithelial ovarian cancer (IEOC) and 611 controls. A baseline interview assessed RPA frequency, intensity, and duration. Each RPA intensity was assigned a metabolic equivalent of task (MET) value and MET-min/week were calculated. Unconditional multivariable logistic regression was performed to investigate associations between RPA and IEOC risk. Compared with sedentary women, predominantly mild intensity RPA was significantly inversely associated with IEOC risk for women reporting above median (>297) MET-min/week (odds ratio [OR] = 0.52; 95% confidence interval [CI]: 0.34, 0.78) and nonsignificantly for <297 MET-min/week (OR = 0.71; 95% CI: 0.44, 1.12). Predominantly moderate intensity RPA was associated with significantly increased risk for women reporting above median (>540) MET-min/week (OR = 1.51; 95% CI: 1.03, 2.23). Predominantly strenuous intensity RPA was nonsignificantly associated with lower IEOC risk for women reporting above median (>1800) MET-min/week (OR = 0.72; 95% CI: 0.33, 1.57). The inverse associations for mild and strenuous intensity RPA were most pronounced in obese women (body mass index >30 kg/m(2) ). The findings that mild and strenuous RPA may reduce the risk of IEOC particularly among obese women are difficult to reconcile with the increased risk observed for moderate RPA. Further research is warranted to determine whether these findings are genuine and, if so, their mechanistic basis.

    View details for DOI 10.1002/cam4.677

    View details for Web of Science ID 000380048700038

    View details for PubMedID 26923432

    View details for PubMedCentralID PMC4924390

  • Polymorphisms risk modeling for vascular toxicity in patients with glioblastoma treated on NRG Oncology/RTOG 0825. Zhou, R., Scheurer, M. E., Gilbert, M. R., Bondy, M., Sulman, E. P., Yuan, Y., Liu, Y., Vera, E., Wendland, M. M., Brachman, D., Bearden, J., McGovern, S., Wilson, S. S., Judy, K. D., Robins, H., Hunter, G., Pugh, S. L., Armstrong, T. S. AMER SOC CLINICAL ONCOLOGY. 2016
  • ASSOCIATIONS OF DIFFERENT FORMS OF PHYSICAL ACTIVITY WITH WEIGHT STATUS IN MEXICAN-ORIGIN ADOLESCENTS Strong, L. L., Forman, M. R., Christie, I. C., Daniel, C. R., Zhao, H., Bondy, M., Wilkinson, A. V. OXFORD UNIV PRESS INC. 2016: S320
  • Assisted Reproductive Technology and Risk of Cancer in Children PEDIATRICS Amirian, E., Bondy, M. L. 2016; 137 (3): e20154509

    View details for DOI 10.1542/peds.2015-4509

    View details for Web of Science ID 000371395800069

    View details for PubMedID 26908680

  • Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Amirian, E., Zhou, R., Wrensch, M. R., Olson, S. H., Scheurer, M. E., Il'yasova, D., Lachance, D., Armstrong, G. N., McCoy, L. S., Lau, C. C., Claus, E. B., Barnholtz-Sloan, J. S., Schildkraut, J., Ali-Osman, F., Sadetzki, S., Johansen, C., Houlston, R. S., Jenkins, R. B., Bernstein, J. L., Merrell, R. T., Davis, F. G., Lai, R., Shete, S., Amos, C. I., Melin, B. S., Bondy, M. L. 2016; 25 (2): 282–90

    Abstract

    Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk.The GICC contains detailed information on history of atopic conditions for 4,533 cases and 4,171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis ORs, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema.Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared with not having respiratory allergies (mOR, 0.72; 95% confidence interval, 0.58-0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma.A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental.As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biologic mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention.

    View details for DOI 10.1158/1055-9965.EPI-15-0847

    View details for Web of Science ID 000372173000008

    View details for PubMedID 26908595

    View details for PubMedCentralID PMC4874516

  • Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer CANCER DISCOVERY Roberts, N. J., Norris, A. L., Petersen, G. M., Bondy, M. L., Brand, R., Gallinger, S., Kurtz, R. C., Olson, S. H., Rustgi, A. K., Schwartz, A. G., Stoffel, E., Syngal, S., Zogopoulos, G., Ali, S. Z., Axilbund, J., Chaffee, K. G., Chen, Y., Cote, M. L., Childs, E. J., Douville, C., Goes, F. S., Herman, J. M., Iacobuzio-Donahue, C., Kramer, M., Makohon-Moore, A., McCombie, R. W., McMahon, K., Niknafs, N., Parla, J., Pirooznia, M., Potash, J. B., Rhim, A. D., Smith, A. L., Wang, Y., Wolfgang, C. L., Wood, L. D., Zandi, P. P., Goggins, M., Karchin, R., Eshleman, J. R., Papadopoulos, N., Kinzler, K. W., Vogelstein, B., Hruban, R. H., Klein, A. P. 2016; 6 (2): 166–75

    Abstract

    Pancreatic cancer is projected to become the second leading cause of cancer-related death in the United States by 2020. A familial aggregation of pancreatic cancer has been established, but the cause of this aggregation in most families is unknown. To determine the genetic basis of susceptibility in these families, we sequenced the germline genomes of 638 patients with familial pancreatic cancer and the tumor exomes of 39 familial pancreatic adenocarcinomas. Our analyses support the role of previously identified familial pancreatic cancer susceptibility genes such as BRCA2, CDKN2A, and ATM, and identify novel candidate genes harboring rare, deleterious germline variants for further characterization. We also show how somatic point mutations that occur during hematopoiesis can affect the interpretation of genome-wide studies of hereditary traits. Our observations have important implications for the etiology of pancreatic cancer and for the identification of susceptibility genes in other common cancer types.The genetic basis of disease susceptibility in the majority of patients with familial pancreatic cancer is unknown. We whole genome sequenced 638 patients with familial pancreatic cancer and demonstrate that the genetic underpinning of inherited pancreatic cancer is highly heterogeneous. This has significant implications for the management of patients with familial pancreatic cancer.

    View details for DOI 10.1158/2159-8290.CD-15-0402

    View details for Web of Science ID 000372323000025

    View details for PubMedID 26658419

    View details for PubMedCentralID PMC4744563

  • The Glioma International Case-Control Study: A Report From the Genetic Epidemiology of Glioma International Consortium AMERICAN JOURNAL OF EPIDEMIOLOGY Amirian, E., Armstrong, G. N., Zhou, R., Lau, C. C., Claus, E. B., Barnholtz-Sloan, J. S., Il'yasova, D., Schildkraut, J., Ali-Osman, F., Sadetzki, S., Johansen, C., Houlston, R. S., Jenkins, R. B., Lachance, D., Olson, S. H., Bernstein, J. L., Merrell, R. T., Wrensch, M. R., Davis, F. G., Lai, R., Shete, S., Amos, C. I., Scheurer, M. E., Aldape, K., Alafuzoff, I., Braennstroem, T., Broholm, H., Collins, P., Giannini, C., Rosenblum, M., Tihan, T., Melin, B. S., Bondy, M. L. 2016; 183 (2): 85–91

    Abstract

    Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen collection. To our knowledge, the GICC Study is the largest glioma study to date that includes collection of blood samples, which will allow for genetic analysis and interrogation of gene-environment interactions.

    View details for DOI 10.1093/aje/kwv235

    View details for Web of Science ID 000369995600001

    View details for PubMedID 26656478

    View details for PubMedCentralID PMC4706682

  • Quantifying the heritability of glioma using genome-wide complex trait analysis SCIENTIFIC REPORTS Kinnersley, B., Mitchell, J. S., Gousias, K., Schramm, J., Idbaih, A., Labussiere, M., Marie, Y., Rahimian, A., Wichmann, H., Schreiber, S., Khe Hoang-Xuan, Delattre, J., Noethen, M. M., Mokhtari, K., Lathrop, M., Bondy, M., Simon, M., Sanson, M., Houlston, R. S. 2015; 5: 17267

    Abstract

    Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) influencing glioma risk. While these SNPs only explain a small proportion of the genetic risk it is unclear how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we applied Genome-Wide Complex Trait Analysis (GCTA) to three GWAS datasets totalling 3,373 cases and 4,571 controls and performed a meta-analysis to estimate the heritability of glioma. Our results identify heritability estimates of 25% (95% CI: 20-31%, P = 1.15 × 10(-17)) for all forms of glioma - 26% (95% CI: 17-35%, P = 1.05 × 10(-8)) for glioblastoma multiforme (GBM) and 25% (95% CI: 17-32%, P = 1.26 × 10(-10)) for non-GBM tumors. This is a substantial increase from the genetic variance identified by the currently identified GWAS risk loci (~6% of common heritability), indicating that most of the heritable risk attributable to common genetic variants remains to be identified.

    View details for DOI 10.1038/srep17267

    View details for Web of Science ID 000365638000001

    View details for PubMedID 26625949

    View details for PubMedCentralID PMC4667278

  • Associations among ancestry, geography and breast cancer incidence, mortality, and survival in Trinidad and Tobago CANCER MEDICINE Warner, W. A., Morrison, R. L., Lee, T. Y., Williams, T. M., Ramnarine, S., Roach, V., Slovacek, S., Maharaj, R., Bascombe, N., Bondy, M. L., Ellis, M. J., Toriola, A. T., Roach, A., Llanos, A. M. 2015; 4 (11): 1742–53

    Abstract

    Breast cancer (BC) is the most common newly diagnosed cancer among women in Trinidad and Tobago (TT) and BC mortality rates are among the highest in the world. Globally, racial/ethnic trends in BC incidence, mortality and survival have been reported. However, such investigations have not been conducted in TT, which has been noted for its rich diversity. In this study, we investigated associations among ancestry, geography and BC incidence, mortality and survival in TT. Data on 3767 incident BC cases, reported to the National Cancer Registry of TT, from 1995 to 2007, were analyzed in this study. Women of African ancestry had significantly higher BC incidence and mortality rates (66.96;30.82 per 100,000) compared to women of East Indian (41.04, MORTALITY: 14.19 per 100,000) or mixed ancestry (36.72, MORTALITY: 13.80 per 100,000). Geographically, women residing in the North West Regional Health Authority (RHA) catchment area followed by the North Central RHA exhibited the highest incidence and mortality rates. Notable ancestral differences in survival were also observed. Women of East Indian and mixed ancestry experienced significantly longer survival than those of African ancestry. Differences in survival by geography were not observed. In TT, ancestry and geographical residence seem to be strong predictors of BC incidence and mortality rates. Additionally, disparities in survival by ancestry were found. These data should be considered in the design and implementation of strategies to reduce BC incidence and mortality rates in TT.

    View details for DOI 10.1002/cam4.503

    View details for Web of Science ID 000365843900014

    View details for PubMedID 26338451

    View details for PubMedCentralID PMC4674001

  • Using a Community-Engaged Approach to Develop a Bilingual Survey about Psychosocial Stressors among Individuals of Mexican Origin JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED Symanski, E., Karpman, M., Jimenez, M., Lopez, D. S., Felknor, S. A., Upadhyaya, M., Strom, S. S., Bondy, M. L. 2015; 26 (4): 1456–71

    Abstract

    Hypertension is on the rise among Hispanics and is highest among those of Mexican origin. Recent studies have found a positive association between air pollution and blood pressure and hypertension. Moreover, a link between hypertension and adverse socioeconomic conditions is well established. However, less is known about psychosocial stressors, although their impact on coronary heart disease has been shown. To address this gap in the literature, community perspectives of the health consequences of environmental exposures and psychosocial stressors experienced among the Mexican-origin population in Houston, Texas were obtained through participation in focus groups, the establishment of a Neighborhood Council of Advisors (NCA), and the testing of a pilot questionnaire. Taken together, the findings from the community were used to develop a culturally sensitive, bilingual questionnaire for an investigation of the combined effects of environmental and psychosocial stressors on hypertension among individuals of Mexican origin.

    View details for DOI 10.1353/hpu.2015.0136

    View details for Web of Science ID 000364799700028

    View details for PubMedID 26548692

  • Genome-wide association study identifies multiple susceptibility loci for glioma NATURE COMMUNICATIONS Kinnersley, B., Labussiere, M., Holroyd, A., Di Stefano, A., Broderick, P., Vijayakrishnan, J., Mokhtari, K., Delattre, J., Gousias, K., Schramm, J., Schoemaker, M. J., Fleming, S. J., Herms, S., Heilmann, S., Schreiber, S., Wichmann, H., Noethen, M. M., Swerdlow, A., Lathrop, M., Simon, M., Bondy, M., Sanson, M., Houlston, R. S. 2015; 6: 8559

    Abstract

    Previous genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of glioma. To identify new glioma susceptibility loci, we conducted a meta-analysis of four GWAS (totalling 4,147 cases and 7,435 controls), with imputation using 1000 Genomes and UK10K Project data as reference. After genotyping an additional 1,490 cases and 1,723 controls we identify new risk loci for glioblastoma (GBM) at 12q23.33 (rs3851634, near POLR3B, P=3.02 × 10(-9)) and non-GBM at 10q25.2 (rs11196067, near VTI1A, P=4.32 × 10(-8)), 11q23.2 (rs648044, near ZBTB16, P=6.26 × 10(-11)), 12q21.2 (rs12230172, P=7.53 × 10(-11)) and 15q24.2 (rs1801591, near ETFA, P=5.71 × 10(-9)). Our findings provide further insights into the genetic basis of the different glioma subtypes.

    View details for DOI 10.1038/ncomms9559

    View details for Web of Science ID 000364932600006

    View details for PubMedID 26424050

    View details for PubMedCentralID PMC4600760

  • Acculturation, Behavioral Factors, and Family History of Breast Cancer among Mexican and Mexican-American Women WOMENS HEALTH ISSUES Nodora, J. N., Cooper, R., Talavera, G. A., Gallo, L., Meza Montenegro, M., Komenaka, I., Natarajan, L., Gutierrez Millan, L., Daneri-Navarro, A., Bondy, M., Brewster, A., Thompson, P., Martinez, M. 2015; 25 (5): 494–500

    Abstract

    Incidence rates for breast cancer are higher among Mexican-American (MA) women in the United States than women living in Mexico. Studies have shown higher prevalence of breast cancer risk factors in more acculturated than less acculturated Hispanic/Latinas in the United States. We compared the prevalence of behavioral risk factors and family history of breast cancer by level of acculturation and country of residence in women of Mexican descent.Data were collected from 1,201 newly diagnosed breast cancer patients living in Mexico (n = 581) and MAs in the United States (n = 620). MA participants were categorized into three acculturation groups (Spanish dominant, bilingual, and English dominant); women living in Mexico were used as the referent group. The prevalence of behavioral risk factors and family history of breast cancer were assessed according to acculturation level, adjusting for age at diagnosis and education.In the adjusted models, bilingual and English-dominant MAs were significantly more likely to have a body mass index of 30 kg/m(2) or greater, consume more than one alcoholic beverage a week, and report having a family history of breast cancer than women living in Mexico. All three U.S. acculturation groups were significantly more likely to have lower total energy expenditure (≤533 kcal/d) than women in Mexico. English-dominant women were significantly less likely to ever smoke cigarettes than the Mexican group.Our findings add to the limited scientific literature on the relationships among acculturation, health behavior, and family history of breast cancer in Mexican and MA women.

    View details for DOI 10.1016/j.whi.2015.05.011

    View details for Web of Science ID 000361060400011

    View details for PubMedID 26189937

    View details for PubMedCentralID PMC4739633

  • Evaluating the Role of Birth Weight and Gestational Age on Acute Lymphoblastic Leukemia Risk Among Those of Hispanic Ethnicity PEDIATRIC HEMATOLOGY AND ONCOLOGY Barahmani, N., Dorak, M., Forman, M. R., Sprehe, M. R., Scheurer, M. E., Bondy, M. L., Okcu, M., Lupo, P. J. 2015; 32 (6): 382–89

    Abstract

    High birth weight is an established risk factor for childhood acute lymphoblastic leukemia (ALL), especially in children younger than 5 years of age at diagnosis. The goal of this study was to explore the association between being born large for gestational age and the risk for ALL by race/ethnicity to determine if the role of this risk factor differed by these characteristics. The authors compared birth certificate data of 575 children diagnosed with ALL who were younger than 5 years and included in the Texas Cancer Registry, Texas Department of Health, between the years 1995 and 2003 with 11,379 controls matched by birth year. Stratified odds ratios were calculated for risk of ALL by birth weight for gestational age, categorized in 3 groups, small, appropriate, and large for gestational age (SGA, AGA, and LGA, respectively), for each race/ethnicity group. The risk of developing ALL was higher among Hispanics who were LGA (odds ratio [OR] = 1.90, 95% confidence interval [CI]: 1.34-2.68) compared with LGA non-Hispanic whites (OR = 1.27, 95% CI: 0.87-1.86) after adjusting for infant gender, year of birth, maternal age, birth order, and presence of Down syndrome. However, the difference was not statistically significant. These results suggest that there may be differences in the association between higher growth in utero and risk of childhood ALL among Hispanics versus non-Hispanic whites.

    View details for DOI 10.3109/08880018.2015.1052867

    View details for Web of Science ID 000369740000003

    View details for PubMedID 26237584

  • Genetic Modulation of Neurocognitive Function in Glioma Patients CLINICAL CANCER RESEARCH Liu, Y., Zhou, R., Sulman, E. P., Scheurer, M. E., Boehling, N., Armstrong, G. N., Tsavachidis, S., Liang, F., Etzel, C. J., Conrad, C. A., Gilbert, M. R., Armstrong, T. S., Bondy, M. L., Wefel, J. S. 2015; 21 (14): 3340–46

    Abstract

    Accumulating evidence supports the contention that genetic variation is associated with neurocognitive function in healthy individuals and increased risk for neurocognitive decline in a variety of patient populations, including cancer patients. However, this has rarely been studied in glioma patients.To identify the effect of genetic variants on neurocognitive function, we examined the relationship between the genotype frequencies of 10,967 single-nucleotide polymorphisms in 580 genes related to five pathways (inflammation, DNA repair, metabolism, cognitive, and telomerase) and neurocognitive function in 233 newly diagnosed glioma patients before surgical resection. Four neuropsychologic tests that measured memory (Hopkins Verbal Learning Test-Revised), processing speed (Trail Making Test A), and executive function (Trail Making Test B, Controlled Oral Word Association) were examined.Eighteen polymorphisms were associated with processing speed and 12 polymorphisms with executive function. For processing speed, the strongest signals were in IRS1 rs6725330 in the inflammation pathway (P = 2.5 × 10(-10)), ERCC4 rs1573638 in the DNA repair pathway (P = 3.4 × 10(-7)), and ABCC1 rs8187858 in metabolism pathway (P = 6.6 × 10(-7)). For executive function, the strongest associations were in NOS1 rs11611788 (P = 1.8 × 10(-8)) and IL16 rs1912124 (P = 6.0 × 10(-7)) in the inflammation pathway, and POLE rs5744761 (P = 6.0 × 10(-7)) in the DNA repair pathway. Joint effect analysis found significant gene polymorphism-dosage effects for processing speed (Ptrend = 9.4 × 10(-16)) and executive function (Ptrend = 6.6 × 10(-15)).Polymorphisms in inflammation, DNA repair, and metabolism pathways are associated with neurocognitive function in glioma patients and may affect clinical outcomes.

    View details for DOI 10.1158/1078-0432.CCR-15-0168

    View details for Web of Science ID 000359324000027

    View details for PubMedID 25904748

    View details for PubMedCentralID PMC4506227

  • Elafin is downregulated during breast and ovarian tumorigenesis but its residual expression predicts recurrence (vol 16, 3417, 2014) BREAST CANCER RESEARCH Caruso, J. A., Karakas, C., Zhang, J., Yi, M., Albarracin, C., Sahin, A., Bondy, M., Liu, J., Hunt, K. K., Keyomarsi, K. 2015; 17: 87

    View details for DOI 10.1186/s13058-015-0572-5

    View details for Web of Science ID 000356774300001

    View details for PubMedID 26108797

    View details for PubMedCentralID PMC4480452

  • A cross-sectional analysis of polycyclic aromatic hydrocarbons and diesel particulate matter exposures and hypertension among individuals of Mexican origin ENVIRONMENTAL HEALTH Bangia, K. S., Symanski, E., Strom, S. S., Bondy, M. 2015; 14: 51

    Abstract

    Epidemiological studies have found that particulate matter is associated with increases in blood pressure. Yet, less is known about the effects of specific sources or constituents of particulate matter, such as diesel particulate matter or polycyclic aromatic hydrocarbons (PAHs). We evaluated associations between self-reported hypertension and residential air levels of diesel particulate matter and PAHs among individuals of Mexican origin living in a large inner city.The Mano a Mano cohort (established in 2001 by the University of Texas MD Anderson Cancer Center) is comprised of individuals of Mexican origin residing in Houston, Texas. Using geographical information systems, we linked modeled annual estimates of PAHs and diesel particulate matter at the census tract level from the 2002 and 2005 U.S. Environmental Protection Agency's National-Scale Air Toxics Assessment to baseline residential addresses of cohort members who enrolled from 2001 to 2003 or 2004 to 2006, respectively. For each enrollment period, we applied mixed-effects logistic regression models to determine associations between diesel particulate matter and PAHs, separately, and self-reported hypertension while adjusting for confounders and the clustering of observations within census tracts and households.The study population consisted of 11218 participants of which 77% were women. The mean participant age at baseline was 41 years. Following adjustment for age, there was a dose-dependent, positive association between PAHs and hypertension (medium exposure, adjusted odds ratio (OR) = 1.09, 95% CI: 0.88-1.36; high exposure, OR = 1.40, 95% CI: 1.01-1.94) for individuals enrolled during 2001-2003; associations were generally similar in magnitude, but less precise, following adjustment for age, gender, smoking, and BMI. No association was detected for the later period. There was no evidence of an association between residential levels of diesel particulate matter and hypertension.This study builds on a limited number of prior investigations of the association between ambient air levels of PAHs or diesel particulate matter and hypertension by focusing on a relatively young cohort of predominantly adult women of Mexican origin. Future analyses are warranted to explore associations in the cohort using incident hypertension when sufficient data become available and to further examine associations between specific chemical constituents of particulate matter and hypertension in this and other populations.

    View details for DOI 10.1186/s12940-015-0039-2

    View details for Web of Science ID 000356651900001

    View details for PubMedID 26068905

    View details for PubMedCentralID PMC4471931

  • Targeted Sequencing in Chromosome 17q Linkage Region Identifies Familial Glioma Candidates in the Gliogene Consortium SCIENTIFIC REPORTS Jalali, A., Amirian, E., Bainbridge, M. N., Armstrong, G. N., Liu, Y., Tsavachidis, S., Jhangiani, S. N., Plon, S. E., Lau, C. C., Claus, E. B., Barnholtz-Sloan, J. S., Il'yasova, D., Schildkraut, J., Ali-Osman, F., Sadetzki, S., Johansen, C., Houlston, R. S., Jenkins, R. B., Lachance, D., Olson, S. H., Bernstein, J. L., Merrell, R. T., Wrensch, M. R., Davis, F. G., Lai, R., Shete, S., Aldape, K., Amos, C. I., Muzny, D. M., Gibbs, R. A., Melin, B. S., Bondy, M. L. 2015; 5: 8278

    Abstract

    Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (<0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned.

    View details for DOI 10.1038/srep08278

    View details for Web of Science ID 000348833600007

    View details for PubMedID 25652157

    View details for PubMedCentralID PMC4317686

  • Germline Mutations in Shelterin Complex Genes Are Associated With Familial Glioma JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Bainbridge, M. N., Armstrong, G. N., Gramatges, M., Bertuch, A. A., Jhangiani, S. N., Doddapaneni, H., Lewis, L., Tombrello, J., Tsavachidis, S., Liu, Y., Jalali, A., Plon, S. E., Lau, C. C., Parsons, D. W., Claus, E. B., Barnholtz-Sloan, J., Il'yasova, D., Schildkraut, J., Ali-Osman, F., Sadetzki, S., Johansen, C., Houlston, R. S., Jenkins, R. B., Lachance, D., Olson, S. H., Bernstein, J. L., Merrell, R. T., Wrensch, M. R., Walsh, K. M., Davis, F. G., Lai, R., Shete, S., Aldape, K., Amos, C. I., Thompson, P. A., Muzny, D. M., Gibbs, R. A., Melin, B. S., Bondy, M. L., Gliogene Consortium 2015; 107 (1)
  • Family history of breast and ovarian cancer and triple negative subtype in hispanic/latina women SPRINGERPLUS Anderson, K., Thompson, P. A., Wertheim, B. C., Martin, L., Komenaka, I. K., Bondy, M., Daneri-Navarro, A., Mercedes Meza-Montenegro, M., Gutierrez-Millan, L., Brewster, A., Madlensky, L., Tobias, M., Natarajan, L., Martinez, M. 2014; 3: 727

    Abstract

    Familial breast and ovarian cancer prevalence was assessed among 1150 women of Mexican descent enrolled in a case-only, binational breast cancer study. Logistic regression was conducted to compare odds of triple negative breast cancer (TNBC) to non-TNBC according to family history of breast and breast or ovarian cancer among 914 of these women. Prevalence of breast cancer family history in a first- and first- or second-degree relative was 13.1% and 24.1%, respectively; that for breast or ovarian cancer in a first-degree relative was 14.9%. After adjustment for age and country of residence, women with a first-degree relative with breast cancer were more likely to be diagnosed with TNBC than non-TNBC (OR=1.98; 95% CI, 1.26-3.11). The odds of TNBC compared to non-TNBC were 1.93 (95% CI, 1.26-2.97) for women with a first-degree relative with breast or ovarian cancer. There were non-significant stronger associations between family history and TNBC among women diagnosed at age <50 compared to ≥50 years for breast cancer in a first-degree relative (P-interaction = 0.14) and a first- or second-degree relative (P-interaction = 0.07). Findings suggest that familial breast cancers are associated with triple negative subtype, possibly related to BRCA mutations in Hispanic/Latina women, which are strongly associated with TNBC. Family history is an important tool to identify Hispanic/Latina women who may be at increased risk of TNBC, and could benefit from prevention and early detection strategies.

    View details for DOI 10.1186/2193-1801-3-727

    View details for Web of Science ID 000359122200002

    View details for PubMedID 25713754

    View details for PubMedCentralID PMC4332916

  • GENETIC MODULATION OF NEUROCOGNITIVE FUNCTION AND OUTCOMES IN GLIOMA PATIENTS Liu, Y., Zhou, R., Sulman, E., Scheurer, M., Boehling, N., Gilbert, M., Armstrong, T., Bondy, M., Wefel, J. OXFORD UNIV PRESS INC. 2014
  • RISK MODELING FOR TEMOZOLOMIDE (TMZ)-MYELOTOXICITY IN PATIENTS WITH GLIOBLASTOMA TREATED ON RTOG 0825 Zhou, R., Scheurer, M., Vera-Bolanos, E., Gilbert, M., Bondy, M., Sulman, E., Hilsenbeck, S., Wendland, M., Brachman, D., Roof, K., Komaki, R., Deutsch, M., Andrews, D., Anderson, B., Lee, R., Pugh, S., Armstrong, T. OXFORD UNIV PRESS INC. 2014
  • Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer NEURO-ONCOLOGY Andersson, U., Wibom, C., Cederquist, K., Aradottir, S., Borg, A., Armstrong, G. N., Shete, S., Lau, C. C., Bainbridge, M. N., Claus, E. B., Barnholtz-Sloan, J., Lai, R., Il'yasova, D., Houlston, R. S., Schildkraut, J., Bernstein, J. L., Olson, S. H., Jenkins, R. B., Lachance, D. H., Wrensch, M., Davis, F. G., Merrell, R., Johansen, C., Sadetzki, S., Bondy, M. L., Melin, B. S., Gliogene Consortium 2014; 16 (10): 1333–40

    Abstract

    Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers.Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer.The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma.We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer.Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes.

    View details for DOI 10.1093/neuonc/nou052

    View details for Web of Science ID 000343671000005

    View details for PubMedID 24723567

    View details for PubMedCentralID PMC4165415

  • Family history and breast cancer subtype: among women of Mexican descent. Anderson, K., Thompson, P., Wertheim, B., Martin, L., Komenaka, I. K., Bondy, M., Daneri-Navarro, A., Meza-Montenegro, M., Gutierrez-Millan, L., Brewster, A. M., Madlensky, L., Martinez, M. AMER SOC CLINICAL ONCOLOGY. 2014
  • GERMLINE REARRANGEMENTS IN FAMILIES WITH STRONG FAMILY HISTORY OF GLIOMA AND MALIGNANT MELANOMA, COLON AND BREAST CANCER Andersson, U., Wibom, C., Cederquist, K., Aradottir, S., Borg, A., Armstrong, G. N., Shete, S., Bondy, M. L., Melin, B. S., Gliogene Consortium OXFORD UNIV PRESS INC. 2014
  • Association between germline single nucleotide polymorphisms in the PI3K-AKT-mTOR pathway, obesity, and breast cancer disease-free survival BREAST CANCER RESEARCH AND TREATMENT Pande, M., Bondy, M. L., Do, K., Sahin, A. A., Ying, J., Mills, G. B., Thompson, P. A., Brewster, A. M. 2014; 147 (2): 381–87

    Abstract

    Obesity-related hormones and cytokines alter PI3 K-AKT-mTOR pathway activation in breast tumors contributing to poorer disease-free survival (DFS) and decreased responsiveness to tamoxifen and trastuzumab. We hypothesized that single nucleotide polymorphisms (SNPs) in candidate genes in the PI3 K-AKT-mTOR signaling pathway may act as genetic modifiers of breast cancer DFS. We analyzed the association of 106 tagging SNPs in 13 genes (ADIPOQ, IGF1, INS, IRS1, LEP, LEPR, LEPROT, PIK3CA, PIK3R5, PTEN, TSC1, TSC2, and AKT1) in the P13K-AKT-mTOR pathway with DFS in a sample of 1,019 women with stage I-II breast cancer. SNPs significantly associated with DFS in any genetic model (additive, dominant, or recessive) after correcting for false discovery rate (FDR = 0.10) were included in Cox proportional hazards multivariable analyses. After adjusting for race/ethnicity, age at diagnosis, tumor stage, and treatment, rs1063539 in ADIPOQ, rs11585329 in LEPR, and rs2519757 in TSC1 were associated with improved DFS, and rs1520220 in IGF1 and rs2677760 in PIK3CA were associated with worse DFS. The associations were not significantly modified by the type of systemic treatment received or body mass index. The SNPs were not associated with tumor characteristics such as tumor size, lymph node status, nuclear grade, or hormone receptor status. In this study, germline SNPs in the PI3 K-AKT-mTOR pathway were associated with breast cancer DFS and may be potential prognostic markers. Future studies are needed to replicate our results and to evaluate the relationship between these polymorphisms and activation of the PI3 K-AKT-mTOR pathway in breast tumors.

    View details for DOI 10.1007/s10549-014-3081-9

    View details for Web of Science ID 000341487600014

    View details for PubMedID 25108739

    View details for PubMedCentralID PMC4174407

  • Bayesian hierarchical structured variable selection methods with application to molecular inversion probe studies in breast cancer JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS Zhang, L., Baladandayuthapani, V., Mallick, B. K., Manyam, G. C., Thompson, P. A., Bondy, M. L., Do, K. 2014; 63 (4): 595–620

    Abstract

    The analysis of alterations that may occur in nature when segments of chromosomes are copied (known as copy number alterations) has been a focus of research to identify genetic markers of cancer. One high-throughput technique recently adopted is the use of molecular inversion probes (MIPs) to measure probe copy number changes. The resulting data consist of high-dimensional copy number profiles that can be used to ascertain probe-specific copy number alterations in correlative studies with patient outcomes to guide risk stratification and future treatment. We propose a novel Bayesian variable selection method, the hierarchical structured variable selection (HSVS) method, which accounts for the natural gene and probe-within-gene architecture to identify important genes and probes associated with clinically relevant outcomes. We propose the HSVS model for grouped variable selection, where simultaneous selection of both groups and within-group variables is of interest. The HSVS model utilizes a discrete mixture prior distribution for group selection and group-specific Bayesian lasso hierarchies for variable selection within groups. We provide methods for accounting for serial correlations within groups that incorporate Bayesian fused lasso methods for within-group selection. Through simulations we establish that our method results in lower model errors than other methods when a natural grouping structure exists. We apply our method to an MIP study of breast cancer and show that it identifies genes and probes that are significantly associated with clinically relevant subtypes of breast cancer.

    View details for DOI 10.1111/rssc.12053

    View details for Web of Science ID 000340178600005

    View details for PubMedID 25705056

    View details for PubMedCentralID PMC4334391

  • Reproductive and Hormonal Risk Profile According to Language Acculturation and Country of Residence in the Ella Binational Breast Cancer Study JOURNAL OF WOMENS HEALTH Nodora, J. N., Gallo, L., Cooper, R., Wertheim, B. C., Natarajan, L., Thompson, P. A., Komenaka, I. K., Brewster, A., Bondy, M., Daneri-Navarro, A., Mercedes Meza-Montenegro, M., Enrique Gutierrez-Millan, L., Martinez, M. 2014; 23 (6): 532–40

    Abstract

    We compared the distribution of breast cancer reproductive and hormonal risk factors by level of acculturation and country of residence in women of Mexican descent.To compare the distribution of breast cancer reproductive and hormonal risk factors by level of acculturation and country of residence in women of Mexican descent, taking into account level of education, we analyzed data on 581 Mexican and 620 Mexican American (MA) women with a history of invasive breast cancer from the Ella Binational Breast Cancer Study. An eight-item language-based acculturation measure was used to classify MA women. Multivariate logistic regression was used to test associations between language acculturation, country of residence, and reproductive and hormonal risk factors.After adjustment for age and education, compared to women residing in Mexico, English-dominant MAs were significantly more likely to have an earlier age at menarche (<12 years; odds ratio [OR]=2.08; 95% confidence interval [CI], 1.30-3.34), less likely to have a late age at first birth (≥30 years; OR=0.49; 95% CI, 0.25-0.97), and less likely to ever breastfeed (OR=0.13; 95% CI, 0.08-0.21).Differences in reproductive and hormonal risk profile according to language acculturation and country of residence are evident; some of these were explained by education. Results support continued efforts to educate Mexican and MA women on screening and early detection of breast cancer along with promotion of modifiable factors, such as breastfeeding.

    View details for DOI 10.1089/jwh.2013.4498

    View details for Web of Science ID 000337222700010

    View details for PubMedID 24475760

    View details for PubMedCentralID PMC4046352

  • Loss of LRIG1 Locus Increases Risk of Early and Late Relapse of Stage I/II Breast Cancer CANCER RESEARCH Thompson, P. A., Ljuslinder, I., Tsavachidis, S., Brewster, A., Sahin, A., Hedman, H., Henriksson, R., Bondy, M. L., Melin, B. S. 2014; 74 (11): 2928–35

    Abstract

    Gains and losses at chromosome 3p12-21 are common in breast tumors and associated with patient outcomes. We hypothesized that the LRIG1 gene at 3p14.1, whose product functions in ErbB-family member degradation, is a critical tumor modifier at this locus. We analyzed 971 stage I/II breast tumors using Affymetrix Oncoscan molecular inversion probe arrays that include 12 probes located within LRIG1. Copy number results were validated against gene expression data available in the public database. By partitioning the LRIG1 probes nearest exon 12/13, we confirm a breakpoint in the gene and show that gains and losses in the subregions differ by tumor and patient characteristics including race/ethnicity. In analyses adjusted for known prognostic factors, loss of LRIG1 was independently associated with risk of any relapse (HR, 1.90; 95% CI, 1.32-2.73), relapse≥5 years (HR, 2.39; 95% CI, 1.31-4.36), and death (HR, 1.55; 95% CI, 1.11-2.16). Analyses of copy number across chromosome 3, as well as expression data from pooled, publicly available datasets, corroborated the hypothesis of an elevated and persistent risk among cases with loss of or low LRIG1. We concluded that loss/low expression of LRIG1 is an independent risk factor for breast cancer metastasis and death in stage I/II patients. Increased hazard in patients with loss/low LRIG1 persists years after diagnosis, suggesting that LRIG1 is acting as a critical suppressor of tumor metastasis and is an early clinical indicator of risk for late recurrences in otherwise low-risk patients.

    View details for DOI 10.1158/0008-5472.CAN-13-2112

    View details for Web of Science ID 000337170600004

    View details for PubMedID 24879564

  • Rising incidence of young-onset colorectal cancer in Texas, 1995-2010. Ying, D., Risser, D. R., Thompson, P., Zarrin-Khameh, N., Bondy, M., Musher, B. AMER SOC CLINICAL ONCOLOGY. 2014
  • Factors influencing recurrence in long-term survivors with early-stage breast cancer of low risk. Pundole, X., Amirian, E., Thompson, P., Brewster, A. M., Bondy, M. AMER SOC CLINICAL ONCOLOGY. 2014
  • Physical Activity Guideline in Mexican-Americans: Does the Built Environment Play a Role? JOURNAL OF IMMIGRANT AND MINORITY HEALTH Oluyomi, A. O., Whitehead, L. W., Burau, K. D., Symanski, E., Kohl, H. W., Bondy, M. 2014; 16 (2): 244–55

    Abstract

    Given disproportionate burden of physical inactivity among US Hispanics and emerging interests in the potential role of the built environment on physical activity, we tested the hypothesis that residing in a more walkable block group is associated with increased physical activity in a cohort of Mexican-American adults. 10,183 Mexican-American adults from Houston, TX, USA were studied. Physical activity was assessed through self-report. Geographical information systems were used to create a "walkability index" (WI). We examined the relationship between WI and physical activity using regression models. Findings for the entire study population suggested a direct association between neighborhood walkability and physical activity that approached statistical significance (High WI vs. Low WI: OR = 1.16; 95% CI 0.95-1.40). Furthermore, participants who lived in a higher WI neighborhood were more likely to meet physical activity guidelines in 2 groups: (1) men whose recreational physical activity included walking (High WI vs. Low WI: OR = 5.43; 95% CI 1.30-22.73) and (2) men whose only recreational physical activity was (High WI vs. Low WI: OR = 9.54; 95% CI 1.84-49.60). Our findings suggest gender differences in the association between the built environment and physical activity in Mexican-American adults. Attempts to encourage walking among Mexican-American adults may be easier in high-walkability neighborhoods than in low-walkability neighborhoods.

    View details for DOI 10.1007/s10903-012-9724-1

    View details for Web of Science ID 000332652800009

    View details for PubMedID 23054541

  • Elafin is downregulated during breast and ovarian tumorigenesis but its residual expression predicts recurrence BREAST CANCER RESEARCH Caruso, J. A., Karakas, C., Zhang, J., Yi, M., Albarracin, C., Sahin, A., Bondy, M., Liu, J., Hunt, K. K., Keyomarsi, K. 2014; 16 (6): 3417

    Abstract

    Elafin is an endogenous serine protease inhibitor. The majority of breast cancer cell lines lack elafin expression compared to human mammary epithelial cells. In this study, we hypothesized that elafin is downregulated during breast and ovarian tumorigenesis.We examined elafin expression by immunohistochemistry (IHC) in specimens of normal breast tissue (n = 24), ductal carcinoma in situ (DCIS) (n = 54), and invasive breast cancer (n = 793). IHC analysis of elafin expression was also performed in normal fallopian tube tissue (n = 20), ovarian cystadenomas (n = 9), borderline ovarian tumors (n = 21), and invasive ovarian carcinomas (n = 216). To understand the significance of elafin in luminal breast cancer cell lines, wild-type or M25G elafin (lacking the protease inhibitory function) were exogenously expressed in MCF-7 and T47D cells.Elafin expression was downregulated in 24% of DCIS and 83% of invasive breast tumors when compared to elafin expression in the normal mammary epithelium. However, the presence of elafin-positive cells in invasive breast tumors, even at low frequency, correlated with poor recurrence-free survival (RFS), reduced overall survival (OS), and clinicopathological markers of aggressive tumor behavior. Elafin-positive cells were an especially strong and independent prognostic marker of reduced RFS in IHC-defined luminal A-like tumors. Elafin was also downregulated in 33% of ovarian cystadenomas, 43% of borderline ovarian tumors, and 86% of invasive ovarian carcinomas when compared to elafin expression in the normal fallopian tube. In ovarian tumors, elafin-positive cells were correlated with reduced RFS, OS and disease-specific survival (DSS) only in stage I/II patients and not in stage III/IV patients. Notably, exogenous expression of elafin or elafin M25G in the luminal breast cancer cell lines MCF-7 and T47D significantly decreased cell proliferation in a protease inhibitory domain-independent manner.Elafin predicts poor outcome in breast and ovarian cancer patients and delineates a subset of endocrine receptor-positive breast cancer patients susceptible to recurrence who could benefit from more aggressive intervention. Our in vitro results suggest that elafin arrests luminal breast cancer cells, perhaps suggesting a role in tumor dormancy.

    View details for DOI 10.1186/s13058-014-0497-4

    View details for Web of Science ID 000349885800034

    View details for PubMedID 25551582

    View details for PubMedCentralID PMC4326485

  • Presence of Viral DNA in Whole-Genome Sequencing of Brain Tumor Tissues from The Cancer Genome Atlas JOURNAL OF VIROLOGY Amirian, E., Bondy, M. L., Mo, Q., Bainbridge, M. N., Scheurer, M. E. 2014; 88 (1): 774

    View details for DOI 10.1128/JVI.02725-13

    View details for Web of Science ID 000329194600075

    View details for PubMedID 24353289

    View details for PubMedCentralID PMC3911725

  • Genomic copy number imbalances associated with bone and non-bone metastasis of early-stage breast cancer BREAST CANCER RESEARCH AND TREATMENT Liu, Y., Zhou, R., Baumbusch, L. O., Tsavachidis, S., Brewster, A. M., Do, K., Sahin, A., Hortobagyi, G. N., Taube, J. H., Mani, S. A., Aaroe, J., Warnberg, F., Borresen-Dale, A., Mills, G. B., Thompson, P. A., Bondy, M. L. 2014; 143 (1): 189–201

    Abstract

    The aim of this study is to identify and validate copy number aberrations in early-stage primary breast tumors associated with bone or non-bone metastasis. Whole-genome molecular inversion probe arrays were used to evaluate copy number imbalances (CNIs) in breast tumors from 960 early-stage patients with information about site of metastasis. The CoxBoost algorithm was used to select metastasis site-related CNIs and to fit a Cox proportional hazards model. Gains at 1q41 and 1q42.12 and losses at 1p13.3, 8p22, and Xp11.3 were significantly associated with bone metastasis. Gains at 2p11.2, 3q21.3-22.2, 3q27.1, 10q23.1, and 14q13.2-3 and loss at 7q21.11 were associated with non-bone metastasis. To examine the joint effect of CNIs and clinical predictors, patients were stratified into three risk groups (low, intermediate, and high) based on the sum of predicted linear hazard ratios. For bone metastasis, the hazard (95 % confidence interval) for the low-risk group was 0.32 (0.11-0.92) compared to the intermediate-risk group and 2.99 (1.74-5.11) for the high-risk group. For non-bone metastasis, the hazard for the low-risk group was 0.34 (0.17-0.66) and 2.33 (1.59-3.43) for the high-risk group. The prognostic value of loss at 8p22 for bone metastasis and gains at 10q23.1 for non-bone metastasis, and gain at 11q13.5 for both bone and non-bone metastases were externally validated in 335 breast tumors pooled from four independent cohorts. Distinct CNIs are independently associated with bone and non-bone metastasis for early-stage breast cancer patients across cohorts. These data warrant consideration for tailoring surveillance and management of metastasis risk.

    View details for DOI 10.1007/s10549-013-2796-3

    View details for Web of Science ID 000329295500019

    View details for PubMedID 24305980

    View details for PubMedCentralID PMC3993091

  • Risk factors for inflammatory breast cancer Atkinson, R. L., Ei-Zein, R. A., Fouad, T. M., de lacerda, L., Wolfe, A. R., Bondy, M. L., Ueno, N. T., Woodward, W. A., Brewster, A. M. AMER ASSOC CANCER RESEARCH. 2013
  • CHROMOSOME 17q LINKAGE SEQUENCING IN FAMILIAL GLIOMA: A REPORT FROM THE GLIOGENE CONSORTIUM Jalali, A., Bainbridge, M., Jhangiani, S., Plon, S. E., Armstrong, G., Bernstein, J., Claus, E., Davis, F., Houlston, R., Il'yasova, D., Jenkins, R., Johansen, C., Lachance, D., Lai, R., Lau, C., Merrell, R., Olson, S. H., Sadetzki, S., Schildkraut, J., Shete, S., Barnholtz-Sloan, J., Wrensch, M., Melin, B., Gibbs, R. A., Bondy, M., Gliogene Consortium OXFORD UNIV PRESS INC. 2013: 90
  • ATOPIC CONDITIONS, ANTIHISTAMINE USE, AND GLIOMA RISK: PRELIMINARY RESULTS FROM THE GLIOMA INTERNATIONAL CASE-CONTROL STUDY Amirian, E., Scheurer, M. E., Wrensch, M., Olson, S. H., Lai, R., Lachance, D., Armstrong, G., Zhou, R., Wiemels, J., Lau, C., Claus, E., Barnholtz-Sloan, J., Il'yasova, D., Schildkraut, J., Houlston, R., Shete, S., Bernstein, J., Jenkins, R., Davis, F., Merrell, R., Johansen, C., Sadetzki, S., Melin, B., Bondy, M., Gliogene Corsortium OXFORD UNIV PRESS INC. 2013: 32
  • POT1 GERMLINE MUTATIONS MAY EXPLAIN A SUBSET OF FAMILIAL GLIOMA: A REPORT FROM THE GLIOGENE CONSORTIUM Bondy, M., Bainbridge, M., Jhangiani, S., Jalali, A., Plon, S. E., Armstrong, G., Bernstein, J., Claus, E., Davis, F., Houlston, R., Il'yasova, D., Jenkins, R., Johansen, C., Lachance, D., Lai, R., Lau, C., Merrell, R., Olson, S., Sadetzki, S., Schildkraut, J., Shete, S., Barnholtz-Sloan, J., Wrensch, M., Melin, B., Gibbs, R. A., Gliogene Consortium OXFORD UNIV PRESS INC. 2013: 89
  • THE FREQUENCY OF THE RS55705857 RISK ALLELE IS ELEVATED AND SIMILAR IN FAMILIAL AND SPORADIC GLIOMA PATIENTS Jenkins, R., Wrensch, M., Kollmeyer, T., Armstrong, G., Olson, S., Lai, R., Lachance, D., Lau, C., Claus, E., Barnholtz-Sloan, J., Il'yasova, D., Schildkraut, J., Houlston, R., Shete, S., Bernstein, J., Davis, F., Merrell, R., Johansen, C., Sadetzki, S., Melin, B., Bondy, M., Gliogene Consortium OXFORD UNIV PRESS INC. 2013: 90
  • Presence of etiologic heterogeneity by breast tumor subtypes in Hispanic women with unique reproductive risk factor patterns Martinez, M., Wertheim, B., Natarajan, L., Schwab, R., Bondy, M., Daneri-Navarro, A., Mercedes Meza-Montenegro, M., Enrique Gutierrez-Millan, L., Brewster, A., Komenaka, I. K., Thompson, P. A. AMER ASSOC CANCER RESEARCH. 2013
  • Prognostic value of the trichorhinophalangeal syndrome-1 (TRPS-1), a GATA family transcription factor, in early-stage breast cancer ANNALS OF ONCOLOGY Chen, J. Q., Bao, Y., Lee, J., Murray, J. L., Litton, J. K., Xiao, L., Zhou, R., Wu, Y., Shen, X. Y., Zhang, H., Sahin, A. A., Katz, R. L., Bondy, M. L., Berinstein, N. L., Hortobagyi, G. N., Radvanyi, L. G. 2013; 24 (10): 2534–42

    Abstract

    TRPS-1 is a new GATA transcription factor that is differentially expressed in breast cancer (BC) where it been found recently to regulate epithelial-to-mesenchymal transition (EMT).We carried out a quantitative immunohistochemistry (qIHC) analysis of TRPS-1 expression in 341 primary-stage I-III BC samples in relation to patient clinical characteristics as well as its prognostic value, especially in an estrogen receptor-positive (ER+) subgroup.Higher TRPS-1 expression was significantly associated with a number of clinical and pathological characteristics as well as with improved overall survival (OS) and disease-free survival (DFS). Among stage I/II ER+ BC patients who received endocrine therapy alone, those with high TRPS-1 expression had significantly longer OS and DFS. There was also a strong association between TRPS-1 levels and the EMT marker E-cadherin in the ER+ invasive ductal carcinoma cases. Analysis of gene expression data on a panel of BC lines found that TRPS-1 expression was low or absent in BC lines having enriched mesenchymal features.Our data indicated that TRPS-1 is an independent prognostic marker in early-stage BC and a new EMT marker that can distinguish patients with ER+ BC who will respond longer to adjuvant endocrine therapy.

    View details for DOI 10.1093/annonc/mdt190

    View details for Web of Science ID 000325153800012

    View details for PubMedID 23729783

    View details for PubMedCentralID PMC3784330

  • Reproductive Factors, Heterogeneity, and Breast Tumor Subtypes in Women of Mexican Descent CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Martinez, M., Wertheim, B. C., Natarajan, L., Schwab, R., Bondy, M., Daneri-Navarro, A., Meza-Montenegro, M., Gutierrez-Millan, L., Brewster, A., Komenaka, I. K., Thompson, P. A. 2013; 22 (10): 1853–61

    Abstract

    Published data support the presence of etiologic heterogeneity by breast tumor subtype, but few studies have assessed this in Hispanic populations.We assessed tumor subtype prevalence and associations between reproductive factors and tumor subtypes in 1,041 women of Mexican descent enrolled in a case-only, binational breast cancer study. Multinomial logistic regression comparing HER2(+) tumors and triple-negative breast cancer (TNBC) to luminal A tumors was conducted.Compared with women with luminal A tumors, those with a later age at first pregnancy were less likely to have TNBC [OR, 0.61; 95% confidence interval (CI), 0.39-0.95], whereas those with three or more full-term pregnancies were more likely to have TNBC (OR, 1.68; 95% CI, 1.10-2.55). A lower odds of TNBC was shown for longer menstruation duration, whether before first pregnancy (OR, 0.78; 95% CI, 0.65-0.93 per 10 years) or menopause (OR, 0.79; 95% CI, 0.69-0.91 per 10 years). Patients who reported breastfeeding for more than 12 months were over twice as likely to have TNBC than luminal A tumors (OR, 2.14; 95% CI, 1.24-3.68). Associations comparing HER2(+) with luminal A tumors were weak or nonexistent except for the interval between last full-term pregnancy and breast cancer diagnosis.Findings show etiologic heterogeneity by tumor subtype in a population of Hispanic women with unique reproductive profiles.Identification of etiologically distinct breast tumor subtypes can further improve our understanding of the disease and help provide personalized prevention and treatment regimens.

    View details for DOI 10.1158/1055-9965.EPI-13-0560

    View details for Web of Science ID 000325631200023

    View details for PubMedID 23950213

    View details for PubMedCentralID PMC3799795

  • Deciphering the 8q24.21 association for glioma HUMAN MOLECULAR GENETICS Enciso-Mora, V., Hosking, F. J., Kinnersley, B., Wang, Y., Shete, S., Zelenika, D., Broderick, P., Idbaih, A., Delattre, J., Hoang-Xuan, K., Marie, Y., Di Stefano, A., Labussiere, M., Dobbins, S., Boisselier, B., Ciccarino, P., Rossetto, M., Armstrong, G., Liu, Y., Gousias, K., Schramm, J., Lau, C., Hepworth, S. J., Strauch, K., Mueller-Nurasyid, M., Schreiber, S., Franke, A., Moebus, S., Eisele, L., Forsti, A., Hemminki, K., Tomlinson, I. P., Swerdlow, A., Lathrop, M., Simon, M., Bondy, M., Sanson, M., Houlston, R. S. 2013; 22 (11): 2293–2302

    Abstract

    We have previously identified tagSNPs at 8q24.21 influencing glioma risk. We have sought to fine-map the location of the functional basis of this association using data from four genome-wide association studies, comprising a total of 4147 glioma cases and 7435 controls. To improve marker density across the 700 kb region, we imputed genotypes using 1000 Genomes Project data and high-coverage sequencing data generated on 253 individuals. Analysis revealed an imputed low-frequency SNP rs55705857 (P = 2.24 × 10(-38)) which was sufficient to fully capture the 8q24.21 association. Analysis by glioma subtype showed the association with rs55705857 confined to non-glioblastoma multiforme (non-GBM) tumours (P = 1.07 × 10(-67)). Validation of the non-GBM association was shown in three additional datasets (625 non-GBM cases, 2412 controls; P = 1.41 × 10(-28)). In the pooled analysis, the odds ratio for low-grade glioma associated with rs55705857 was 4.3 (P = 2.31 × 10(-94)). rs55705857 maps to a highly evolutionarily conserved sequence within the long non-coding RNA CCDC26 raising the possibility of direct functionality. These data provide additional insights into the aetiological basis of glioma development.

    View details for DOI 10.1093/hmg/ddt063

    View details for Web of Science ID 000319432000015

    View details for PubMedID 23399484

    View details for PubMedCentralID PMC3652416

  • The Childhood Leukemia International Consortium CANCER EPIDEMIOLOGY Metayer, C., Milne, E., Clavel, J., Infante-Rivard, C., Petridou, E., Taylor, M., Schuez, J., Spector, L. G., Dockerty, J. D., Magnani, C., Pombo-de-Oliveira, M. S., Sinnett, D., Murphy, M., Roman, E., Monge, P., Ezzat, S., Mueller, B. A., Scheurer, M. E., Armstrong, B. K., Birch, J., Kaatsch, P., Koifman, S., Lightfoot, T., Bhatti, P., Bondy, M. L., Rudant, J., O'Neill, K., Miligi, L., Dessypris, N., Kang, A. Y., Buffler, P. A. 2013; 37 (3): 336–47

    Abstract

    Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemia (ALL) and 17% are acute myeloid leukemia (AML). Childhood leukemia shows further diversity based on cytogenetic and molecular characteristics, which may relate to distinct etiologies. Case-control studies conducted worldwide, particularly of ALL, have collected a wealth of data on potential risk factors and in some studies, biospecimens. There is growing evidence for the role of infectious/immunologic factors, fetal growth, and several environmental factors in the etiology of childhood ALL. The risk of childhood leukemia, like other complex diseases, is likely to be influenced both by independent and interactive effects of genes and environmental exposures. While some studies have analyzed the role of genetic variants, few have been sufficiently powered to investigate gene-environment interactions.The Childhood Leukemia International Consortium (CLIC) was established in 2007 to promote investigations of rarer exposures, gene-environment interactions and subtype-specific associations through the pooling of data from independent studies.By September 2012, CLIC included 22 studies (recruitment period: 1962-present) from 12 countries, totaling approximately 31000 cases and 50000 controls. Of these, 19 case-control studies have collected detailed epidemiologic data, and DNA samples have been collected from children and child-parent trios in 15 and 13 of these studies, respectively. Two registry-based studies and one study comprising hospital records routinely obtained at birth and/or diagnosis have limited interview data or biospecimens.CLIC provides a unique opportunity to fill gaps in knowledge about the role of environmental and genetic risk factors, critical windows of exposure, the effects of gene-environment interactions and associations among specific leukemia subtypes in different ethnic groups.

    View details for DOI 10.1016/j.canep.2012.12.011

    View details for Web of Science ID 000318677600022

    View details for PubMedID 23403126

    View details for PubMedCentralID PMC3652629

  • Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222 BRITISH JOURNAL OF CANCER Enciso-Mora, V., Hosking, F. J., Di Stefano, A. L., Zelenika, D., Shete, S., Broderick, P., Idbaih, A., Delattre, J., Hoang-Xuan, K., Marie, Y., Labussiere, M., Alentorn, A., Ciccarino, P., Rossetto, M., Armstrong, G., Liu, Y., Gousias, K., Schramm, J., Lau, C., Hepworth, S. J., Schoemaker, M., Strauch, K., Mueller-Nurasyid, M., Schreiber, S., Franke, A., Moebus, S., Eisele, L., Swerdlow, A., Simon, M., Bondy, M., Lathrop, M., Sanson, M., Houlston, R. S. 2013; 108 (10): 2178–85

    Abstract

    Most of the heritable risk of glioma is presently unaccounted for by mutations in known genes. In addition to rare inactivating germline mutations in TP53 causing glioma in the context of the Li-Fraumeni syndrome, polymorphic variation in TP53 may also contribute to the risk of developing glioma.To comprehensively evaluate the impact of variation in TP53 on risk, we analysed 23 tagSNPs and imputed 2377 unobserved genotypes in four series totaling 4147 glioma cases and 7435 controls.The strongest validated association signal was shown by the imputed single-nucleotide polymorphism (SNP) rs78378222 (P=6.86 × 10(-24), minor allele frequency ~0.013). Confirmatory genotyping confirmed the high quality of the imputation. The association between rs78378222 and risk was seen for both glioblastoma multiforme (GBM) and non-GBM tumours. We comprehensively examined the relationship between rs78378222 and overall survival in two of the case series totaling 1699 individuals. Despite employing statistical tests sensitive to the detection of differences in early survival, no association was shown.Our data provided strong validation of rs78378222 as a risk factor for glioma but do not support the tenet that the polymorphism being a clinically useful prognostic marker. Acquired TP53 inactivation is a common feature of glioma. As rs78378222 changes the polyadenylation signal of TP53 leading to impaired 3'-end processing of TP53 mRNA, the SNP has strong plausibility for being directly functional contributing to the aetiological basis of glioma.

    View details for DOI 10.1038/bjc.2013.155

    View details for Web of Science ID 000319561300033

    View details for PubMedID 23571737

    View details for PubMedCentralID PMC3670481

  • The Relationship Between Eight GWAS-Identified Single-Nucleotide Polymorphisms and Primary Breast Cancer Outcomes ONCOLOGIST Bayraktar, S., Thompson, P. A., Yoo, S., Do, K., Sahin, A. A., Arun, A. K., Bondy, M. L., Brewster, A. M. 2013; 18 (5): 493–500

    Abstract

    Several single-nucleotide polymorphisms (SNPs) associated with breast cancer risk have been identified through genome-wide association studies (GWAS). We investigated whether eight risk SNPs identified in GWAS were associated with breast cancer disease-free survival (DFS) and overall survival (OS) rates.A cohort of 739 white women with early-stage breast cancer was genotyped for eight GWAS-identified SNPs (rs2981582, rs1219648 [FGFR2], rs3803662, rs12443621, rs8051542 [TOX3], rs999737 [RAD51L1], rs6504950 [17q23], and rs4973768 [3p24]). Relationships between SNPs and breast cancer outcomes were evaluated using Cox proportional hazard regression models. The cumulative effects of SNPs on breast cancer outcomes were assessed by computing the number of at-risk genotypes.At a median follow-up of 121 months (range: 188-231 months) for survivors, 237 deaths (32%) and 186 breast cancer events (25%) were identified among the 739 patients. After adjusting for age, clinical stage, and treatment, rs12443621 (16q12; p = .03) and rs6504950 (17q23; p = .008) were prognostic for OS but not DFS. A higher risk for death was also found in the multivariable analysis of patients harboring three or four at-risk genotypes of the GWAS SNPs compared to patients carrying two or less at-risk genotypes (hazard ratio: 1.60, 95% confidence interval: 1.23-2.24; p = .0008).The study results suggest that previously identified breast cancer risk susceptibility loci, rs12443621 (16q12) and rs6504950 (17q23), may influence breast cancer prognosis or comorbid conditions associated with overall survival. The precise molecular mechanisms through which these risk SNPs, as well as others that were not included in the analysis, influence clinical outcomes remain to be determined.

    View details for DOI 10.1634/theoncologist.2012-0419

    View details for Web of Science ID 000319555600004

    View details for PubMedID 23635555

    View details for PubMedCentralID PMC3662839

  • Description of selected characteristics of familial glioma patients - Results from the Gliogene Consortium EUROPEAN JOURNAL OF CANCER Sadetzki, S., Bruchim, R., Oberman, B., Armstrong, G. N., Lau, C. C., Claus, E. B., Barnholtz-Sloan, J. S., Il'yasova, D., Schildkraut, J., Johansen, C., Houlston, R. S., Shete, S., Amos, C. I., Bernstein, J. L., Olson, S. H., Jenkins, R. B., Lachance, D., Vick, N. A., Merrell, R., Wrensch, M., Davis, F. G., McCarthy, B. J., Lai, R., Melin, B. S., Bondy, M. L., Gliogene Consortium 2013; 49 (6): 1335–45

    Abstract

    While certain inherited syndromes (e.g. Neurofibromatosis or Li-Fraumeni) are associated with an increased risk of glioma, most familial gliomas are non-syndromic. This study describes the demographic and clinical characteristics of the largest series of non-syndromic glioma families ascertained from 14 centres in the United States (US), Europe and Israel as part of the Gliogene Consortium.Families with 2 or more verified gliomas were recruited between January 2007 and February 2011. Distributions of demographic characteristics and clinical variables of gliomas in the families were described based on information derived from personal questionnaires.The study population comprised 841 glioma patients identified in 376 families (9797 individuals). There were more cases of glioma among males, with a male to female ratio of 1.25. In most families (83%), 2 gliomas were reported, with 3 and 4 gliomas in 13% and 3% of the families, respectively. For families with 2 gliomas, 57% were among 1st-degree relatives, and 31.5% among 2nd-degree relatives. Overall, the mean (±standard deviation [SD]) diagnosis age was 49.4 (±18.7) years. In 48% of families with 2 gliomas, at least one was diagnosed at <40y, and in 12% both were diagnosed under 40y of age. Most of these families (76%) had at least one grade IV glioblastoma multiforme (GBM), and in 32% both cases were grade IV gliomas. The most common glioma subtype was GBM (55%), followed by anaplastic astrocytoma (10%) and oligodendroglioma (8%). Individuals with grades I-II were on average 17y younger than those with grades III-IV.Familial glioma cases are similar to sporadic cases in terms of gender distribution, age, morphology and grade. Most familial gliomas appear to comprise clusters of two cases suggesting low penetrance, and that the risk of developing additional gliomas is probably low. These results should be useful in the counselling and clinical management of individuals with a family history of glioma.

    View details for DOI 10.1016/j.ejca.2012.11.009

    View details for Web of Science ID 000317188600020

    View details for PubMedID 23290425

    View details for PubMedCentralID PMC3615132

  • Association Between Parity and Obesity in Mexican and Mexican-American Women: Findings from the Ella Binational Breast Cancer Study JOURNAL OF IMMIGRANT AND MINORITY HEALTH Martinez, M., Pond, E., Wertheim, B. C., Nodora, J. N., Jacobs, E. T., Bondy, M., Daneri-Navarro, A., Mercedes Meza-Montenegro, M., Enrique Gutierrez-Millan, L., Brewster, A., Komenaka, I. K., Thompson, P. 2013; 15 (2): 234–43

    Abstract

    Obesity at diagnosis of breast cancer is associated with higher all-cause mortality and treatment-associated toxicities. We evaluated the association between parity and obesity in the Ella study, a population of Mexican and Mexican-American breast cancer patients with high parity. Obesity outcomes included body mass index (BMI) ≥30 kg/m(2), waist circumference (WC) ≥35 in (88 cm), and waist-to-hip-ratio (WHR) ≥0.85. Prevalence of obesity ([BMI] ≥ 30 kg/m(2)) was 38.9 %. For WC, the multivariate odds ratio (OR) (95 % confidence interval [CI]) for having WC ≥ 35 inches in women with ≥4 pregnancies relative to those with 1-2 pregnancies was 1.59 (1.01-2.47). Higher parity (≥4 pregnancies) was non-significantly associated with high BMI (OR = 1.10; 95 % CI 0.73-1.67). No positive association was observed for WHR. Our results suggest WC is independently associated with high parity in Hispanic women and may be an optimal target for post-partum weight loss interventions.

    View details for DOI 10.1007/s10903-012-9649-8

    View details for Web of Science ID 000321239800002

    View details for PubMedID 22618357

    View details for PubMedCentralID PMC3469728

  • Prognostic value of single nucleotide polymorphisms of candidate genes associated with inflammation in early stage breast cancer BREAST CANCER RESEARCH AND TREATMENT Murray, J. L., Thompson, P., Yoo, S., Kim-Anh Do, Pande, M., Zhou, R., Liu, Y., Sahin, A. A., Bondy, M. L., Brewster, A. M. 2013; 138 (3): 917–24

    Abstract

    To examine the role of germline genetic variations in inflammatory pathways as modifiers of time to recurrence (TTR) in patients with early stage breast cancer (BC), DNA from 997 early stage BC patients was genotyped for 53 tagging single nucleotide polymorphisms (SNPs) in 12 genes involved in inflammation. SNPs were analyzed separately for Caucasians versus African-Americans and Hispanics. Cox proportional hazards models were used to evaluate the association between SNPs in the inflammatory genes and TTR, adjusted for clinical and pathologic covariates. In univariable analyses of Caucasian women, the homozygous genotype of 12 SNPs, including 6 NFKB1 SNPs, 4 IL4 SNPs, and 2 IL13 SNPs, were significantly associated with a decrease in TTR compared with the heterozygous and/or corresponding homozygous genotype (P < 0.05). The significant NFKB1 and IL4 SNPs were in an area of high linkage disequilibrium (D' > 0.8). After adjusting for stage, age, and treatment, carriage of the homozygous genotypes for NFKB1 rs230532 and IL13rs1800925 were independently associated with a shorter TTR (P = 0.001 and P = 0.034, respectively). In African-American and Hispanic patients, expression of NFKB1 rs3774932, TNFrs1799964, and IL4rs3024543 SNPs were associated with a shorter TTR in univariable model. Only NFKB1 rs3774932 (P = 0.02) and IL4Rrs3024543 (P = 0.03) had independent prognostic value in the multivariable model These data support the existence of host genetic susceptibility as a component in recurrence risk mediated by pro-inflammatory and immune factors, and suggest the potential for drugs which modify immune responses and inflammatory genes to improve prognosis in early stage BC.

    View details for DOI 10.1007/s10549-013-2445-x

    View details for Web of Science ID 000317977300026

    View details for PubMedID 23529385

    View details for PubMedCentralID PMC3746974

  • High risk CNIs, race and early stage breast cancer Thompson, P. A., Brewster, A., Do, K., Sahin, A. A., Mills, G., Bondy, M. FEDERATION AMER SOC EXP BIOL. 2013
  • Genetic variants in the vitamin D pathway and breast cancer disease-free survival CARCINOGENESIS Pande, M., Thompson, P. A., Do, K., Sahin, A. A., Amos, C. I., Frazier, M. L., Bondy, M. L., Brewster, A. M. 2013; 34 (3): 587–94

    Abstract

    Epidemiological studies have investigated the association between vitamin D pathway genes and breast cancer risk; however, little is known about the association between vitamin D pathway genes and breast cancer prognosis. In a retrospective cohort of 1029 patients with early-stage breast cancer, we analyzed the association between 106 tagging single nucleotide polymorphisms (SNPs) in eight vitamin D pathway genes and breast cancer disease-free survival (DFS) using Cox regression analysis adjusted for known prognostic variables. Using a false discovery rate of 10%, six intronic SNPs were significantly associated with poorer DFS: retinoid-X receptor alpha (RXRA) SNPs (rs881658, rs11185659, rs10881583, rs881657 and rs7864987) and plasminogen activator and urokinase receptor (PLAUR) SNP (rs4251864). Treatment received (no systemic therapy, hormone therapy alone or chemotherapy) was an effect modifier of the RXRA SNPs association with DFS (P < 0.05); therefore, we stratified further analysis by treatment group. Among patients who did not receive systemic therapy, RXRA SNP [rs10881583 (P = 0.02)] was associated with poorer DFS, and among patients who received chemotherapy, RXRA SNPs (rs881658, rs11185659, rs10881583, rs881657 and rs7864987) were associated with poorer DFS (P < 0.001 for all SNPs). However, RXRA SNPs: rs10881583 (P < 0.001) and rs881657 (P = 0.02) were associated with improved DFS in patients treated with hormone therapy alone. Our results suggest that SNPs in the RXRA and PLAUR genes in the vitamin D pathway may contribute to breast cancer DFS. In particular, SNPs in RXRA may predict for poorer or improved DFS in patients, according to type of systemic treatment received. If validated, these markers could be used for risk stratification of breast cancer patients.

    View details for DOI 10.1093/carcin/bgs369

    View details for Web of Science ID 000315629000011

    View details for PubMedID 23180655

    View details for PubMedCentralID PMC3581599

  • Sensation-seeking genes and physical activity in youth GENES BRAIN AND BEHAVIOR Wilkinson, A. V., Gabriel, K. P., Wang, J., Bondy, M. L., Dong, Q., Wu, X., Shete, S., Spitz, M. R. 2013; 12 (2): 181–88

    Abstract

    Many studies examining genetic influences on physical activity (PA) have evaluated the impact of single nucleotide polymorphisms (SNPs) related to the development of lifestyle-related chronic diseases, under the hypothesis that they would be associated with PA. However, PA is a multidetermined behavior and associated with a multitude of health consequences. Thus, examining a broader range of candidate genes associated with a broader range of PA correlates may provide new insights into the genetic underpinnings of PA. In this study, we focus on one such correlate - sensation-seeking behavior. Participants (N = 1130 Mexican origin youth) provided a saliva sample and data on PA and sensation-seeking tendencies in 2008-2009. Participants were genotyped for 630 functional and tagging variants in the dopamine, serotonin and cannabinoid pathways. Overall 30% of participants (males - 37.6% and females - 22.0%) reported ≥60 min of PA on 5 of 7 days. After adjusting for gender, age and population stratification, and applying the Bayesian False Discovery Probability approach for assessing noteworthiness, four gene variants were significantly associated with PA. In a multivariable model, being male, having higher sensation-seeking tendencies and at least one copy of the minor allele for SNPs in angiotensin I-converting enzyme gene [ACE; rs8066276 odds ratio (OR) = 1.44; P = 0.012] and tryptophan hydroxylase 2 gene (TPH2; rs11615016 OR = 1.73; P = 0.021) were associated with increased likelihood of meeting PA recommendations. Participants with at least one copy of the minor allele for SNPs in synaptosomal-associated protein 25 gene (SNAP25; rs363035 OR = 0.53; P = 0.005) and cannabinoid receptor 1 gene (CNR1; rs6454672 OR = 0.62; P = 0.022) have decreased likelihood of meeting PA recommendations. Our findings extend current knowledge of the complex relationship between PA and possible genetic underpinnings.

    View details for DOI 10.1111/gbb.12006

    View details for Web of Science ID 000315957400003

    View details for PubMedID 23190435

    View details for PubMedCentralID PMC3581711

  • Anti-human-cytomegalovirus immunoglobulin G levels in glioma risk and prognosis CANCER MEDICINE Amirian, E., Marquez-Do, D., Bondy, M. L., Scheurer, M. E. 2013; 2 (1): 57–62

    Abstract

    The role of human cytomegalovirus (HCMV) in glioma development and progression remains controversial. The purpose of our study was to assess the potential associations between anti-HCMV antibodies (immunoglobulin G [IgG] and immunoglobulin M [IgM]) and glioma risk and prognosis using data from the Harris County Case-Control Study. Multivariable logistic regression models were utilized to estimate odds ratios and 95% confidence intervals (CI) for the associations between glioma status and antibody levels among glioma cases (n = 362) and cancer-free controls (n = 462). Hazard ratios and 95% CIs were calculated using Cox proportional hazards regression, adjusting for age, race, and sex, to determine if antibody levels were associated with survival over time among cases. Among IgG-positive participants, increasing anti-HCMV IgG levels were associated with decreasing glioma risk (P for trend = 0.0008), and those with the lowest level of anti-HCMV IgG (<10 U/mL) had the highest glioma risk, controlling for age, sex, and race/ethnicity (OR: 2.51, 95% CI: 1.42-4.43). Antibody levels were not associated with survival among glioma cases. Our study contributes new evidence toward the potential importance of the direct and indirect effects of HCMV infection in gliomagenesis.

    View details for DOI 10.1002/cam4.44

    View details for Web of Science ID 000209210500007

    View details for PubMedID 24133628

    View details for PubMedCentralID PMC3797564

  • Changes in body mass index and alcohol and tobacco consumption among breast cancer survivors and cancer-free women: A prospective study in the Danish Diet, Cancer and Health Cohort ACTA ONCOLOGICA Bidstrup, P. E., Dalton, S. O., Christensen, J., Tjonneland, A., Larsen, S. B., Karlsen, R., Brewster, A., Bondy, M., Johansen, C. 2013; 52 (2): 327–35

    Abstract

    A breast cancer diagnosis has been suggested as a teachable moment when a woman is more open to making healthier lifestyle changes. Little is known about the health behaviour changes women with breast cancer initiate compared to those made by other women.We examined changes in body mass index (BMI) and tobacco and alcohol consumption among women with a diagnosis of breast cancer and among cancer-free women. We used data from 23 420 women aged 50-64 years who participated in the Diet, Cancer and Health cohort, of whom 449 were diagnosed with breast cancer between baseline (1993-1997) and follow-up (2000-2002), and 22 971 remained cancer-free. We used multiple linear regression analysis to examine differences in BMI and alcohol and tobacco consumption between the two groups and to examine whether demographic and prognostic factors were associated with behavioural changes in women with breast cancer.There were no significant differences in changes in BMI, alcohol and tobacco consumption between the two groups. Only in sub-analyses among women who lost weight between baseline and follow-up, women with breast cancer lost more weight than cancer-free women (β = 0.2; CI 0.1; 0.4), but residual confounding from stage cannot be excluded. Among the women with breast cancer we found no significant changes in BMI, alcohol and tobacco consumption by level of education, marital status, chemotherapy, hormone therapy or radiation.Women with breast cancer did not reduce their BMI, or modify their alcohol use or tobacco consumption compared with cancer-free women. This study indicates that guidelines and interventions to change health behaviour are needed after a cancer diagnosis.

    View details for DOI 10.3109/0284186X.2012.746466

    View details for Web of Science ID 000313672800016

    View details for PubMedID 23244678

  • Eliminating second-hand smoke from Mexican-American households: Outcomes from Project Clean Air-Safe Air (CASA) ADDICTIVE BEHAVIORS Prokhorov, A. V., Hudmon, K., Marani, S. K., Bondy, M. L., Gatus, L. A., Spitz, M. R., Wilkinson, A. V., Hammond, S., Koehly, L. M. 2013; 38 (1): 1485–92

    Abstract

    Exposure to second-hand smoke (SHS) is a major public health problem and a risk factor for morbidity and mortality. The objective of this randomized trial was to estimate the impact of a culturally-sensitive intervention to reduce SHS exposure in Mexican-American households.A total of 91 households (with a child under 18 years of age and two adults, one of whom was a smoker) were recruited from a population-based cohort of Mexican-American households and randomized to receive the experimental intervention (EI; n=47) or standard care (SC; n=44). Of these, 74 households (83%) provided baseline, 6-month, and 12-month survey and nicotine monitor data (EI, n=39; SC, n=35). The EI materials, designed to increase the participants' likelihood of adopting a smoke-free indoor home air policy, included one culturally-appropriate bilingual comic book for children and two fotonovelas for adults.Ambient nicotine levels significantly decreased over the 12 study months (F=13.6, DF=147; p<0.001); with a significantly greater decrease in the EI households compared to the SC households (F=4.1, DF=72; p<0.05). At 12 months, 73% of EI households had banned smoking vs. 56% of SC households. Ambient nicotine levels, measured using nicotine air sampling monitors, were significantly associated with self-reported SHS exposure at the 12-month follow-up. Knowledge of the health effects of SHS increased from baseline to 6 and 12 months in the EI condition but not in the SC condition (F=6.0, DF=238; p<0.01), and smokers and quitters in the EI group reported an increased perception of health vulnerability compared to those in the SC group.Our low-cost intervention impacted SHS-related knowledge and exposure among Mexican Americans. This culturally-appropriate intervention has the potential to decrease SHS-related health problems in the target population substantially.

    View details for DOI 10.1016/j.addbeh.2012.06.023

    View details for Web of Science ID 000312358300013

    View details for PubMedID 23085392

    View details for PubMedCentralID PMC6009833

  • Frequency of mesenchymal-epithelial transition factor gene (MET) and the catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevation and correlation with outcome in patients with early stage breast cancer CANCER Gonzalez-Angulo, A. M., Chen, H., Karuturi, M. S., Chavez-MacGregor, M., Tsavachidis, S., Meric-Bernstam, F., Do, K., Hortobagyi, G. N., Thompson, P. A., Mills, G. B., Bondy, M. L., Blumenschein, G. R. 2013; 119 (1): 7–15

    Abstract

    The current study was conducted to determine the frequency and association between recurrence-free survival (RFS) and MET and catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevations in patients with early stage breast cancer.Tumor DNA was extracted from 971 formalin-fixed, paraffin-embedded early breast cancers for molecular inversion probes arrays. Data were segmented using the single-nucleotide polymorphism (SNP)-FASST2 segmentation algorithm. Copy number gains were called when the copy number of each segment was greater than 2.3 or 1.7, respectively. RFS was estimated by the Kaplan-Meier method. Cox proportional hazards models were fit to determine independent associations between copy number and RFS.Of the 971 tumors studied, 82 (8.44%) and 134 (13.8%) had an elevation of the MET or PIK3CA copy number, respectively, and 25.6% of tumors with a MET copy number elevation had a PIK3CA copy number elevation. Patients with either a MET or PI3KCA high copy number tended to have poorer prognostic features (larger tumor size, higher tumor grade, and hormone receptor negativity). Both MET and PIK3CA high copy numbers were more likely to occur in patients with triple receptor-negative disease (P = .019 and P < .001, respectively). At a median follow-up of 7.4 years, there were 252 cases of disease recurrence. The 5-year RFS rates were 63.5% and 83.1% for MET high copy number and MET normal/low copy number, respectively (P = .06) and 73.1%, and 82.3% for PIK3CA high copy number and PIK3CA normal/low copy number, respectively (P = .15). A high copy number for either gene was not found to be an independent predictor of RFS.A high copy number of MET or PIK3CA was found to be associated with poorer prognostic features and triple receptor-negative disease. Coamplification was frequent. Patients with tumors with high MET copy numbers tended to have a worse RFS.

    View details for DOI 10.1002/cncr.27608

    View details for Web of Science ID 000312543000005

    View details for PubMedID 22736407

    View details for PubMedCentralID PMC3461089

  • Hypothesized role of pregnancy hormones on HER2+breast tumor development BREAST CANCER RESEARCH AND TREATMENT Cruz, G. I., Martinez, M., Natarajan, L., Wertheim, B. C., Gago-Dominguez, M., Bondy, M., Daneri-Navarro, A., Mercedes Meza-Montenegro, M., Enrique Gutierrez-Millan, L., Brewster, A., Schedin, P., Komenaka, I. K., Esteban Castelao, J., Carracedo, A., Redondo, C. M., Thompson, P. A. 2013; 137 (1): 237–46

    Abstract

    Breast cancer incidence rates have declined among older but not younger women; the latter are more likely to be diagnosed with breast cancers carrying a poor prognosis. Epidemiological evidence supports an increase in breast cancer incidence following pregnancy with risk elevated as much as 10 years post-partum. We investigated the association between years since last full-term pregnancy at the time of diagnosis (≤10 or >10 years) and breast tumor subtype in a case series of premenopausal Hispanic women (n = 627). Participants were recruited in the United States, Mexico, and Spain. Cases with known estrogen receptor (ER), progesterone receptor (PR), and HER2 status, with one or more full-term pregnancies ≥1 year prior to diagnosis were eligible for this analysis. Cases were classified into three tumor subtypes according to hormone receptor (HR+ = ER+ and/or PR+; HR- = ER- and PR-) expression and HER2 status: HR+/HER2-, HER2+ (regardless of HR), and triple negative breast cancer. Case-only odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for HER2+ tumors in reference to HR+/HER2- tumors. Participants were pooled in a mixed-effects logistic regression model with years since pregnancy as a fixed effect and study site as a random effect. When compared to HR+/HER2- cases, women with HER2+ tumors were more likely be diagnosed in the post-partum period of ≤10 years (OR = 1.68; 95 % CI, 1.12-2.52). The effect was present across all source populations and independent of the HR status of the HER2+ tumor. Adjusting for age at diagnosis (≤45 or >45 years) did not materially alter our results (OR = 1.78; 95 % CI, 1.08-2.93). These findings support the novel hypothesis that factors associated with the post-partum breast, possibly hormonal, are involved in the development of HER2+ tumors.

    View details for DOI 10.1007/s10549-012-2313-0

    View details for Web of Science ID 000312710500022

    View details for PubMedID 23135573

    View details for PubMedCentralID PMC4054812

  • Methods for the Analysis of Copy Number Data in Cancer Research ADVANCES IN STATISTICAL BIOINFORMATICS: MODELS AND INTEGRATIVE INFERENCE FOR HIGH-THROUGHPUT DATA Broom, B. M., Do, K., Bondy, M., Thompson, P., Coombes, K., Do, K. A., Qin, Z. S., Vannucci, M. 2013: 244–71
  • A Variable Age of Onset Segregation Model for Linkage Analysis, with Correction for Ascertainment, Applied to Glioma CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Sun, X., Vengoechea, J., Elston, R., Chen, Y., Amos, C. I., Armstrong, G., Bernstein, J. L., Claus, E., Davis, F., Houlston, R. S., Il'yasova, D., Jenkins, R. B., Johansen, C., Lai, R., Lau, C. C., Liu, Y., McCarthy, B. J., Olson, S. H., Sadetzki, S., Schildkraut, J., Shete, S., Yu, R., Vick, N. A., Merrell, R., Wrensch, M., Yang, P., Melin, B., Bondy, M. L., Barnholtz-Sloan, J. S., Gliogene Consortium 2012; 21 (12): 2242–51

    Abstract

    We propose a 2-step model-based approach, with correction for ascertainment, to linkage analysis of a binary trait with variable age of onset and apply it to a set of multiplex pedigrees segregating for adult glioma.First, we fit segregation models by formulating the likelihood for a person to have a bivariate phenotype, affection status and age of onset, along with other covariates, and from these we estimate population trait allele frequencies and penetrance parameters as a function of age (N = 281 multiplex glioma pedigrees). Second, the best fitting models are used as trait models in multipoint linkage analysis (N = 74 informative multiplex glioma pedigrees). To correct for ascertainment, a prevalence constraint is used in the likelihood of the segregation models for all 281 pedigrees. Then the trait allele frequencies are reestimated for the pedigree founders of the subset of 74 pedigrees chosen for linkage analysis.Using the best-fitting segregation models in model-based multipoint linkage analysis, we identified 2 separate peaks on chromosome 17; the first agreed with a region identified by Shete and colleagues who used model-free affected-only linkage analysis, but with a narrowed peak: and the second agreed with a second region they found but had a larger maximum log of the odds (LOD).Our approach was able to narrow the linkage peak previously published for glioma.We provide a practical solution to model-based linkage analysis for disease affection status with variable age of onset for the kinds of pedigree data often collected for linkage analysis.

    View details for DOI 10.1158/1055-9965.EPI-12-0703

    View details for Web of Science ID 000312280800013

    View details for PubMedID 22962404

    View details for PubMedCentralID PMC3518573

  • Genome-wide association study of glioma and meta-analysis HUMAN GENETICS Rajaraman, P., Melin, B. S., Wang, Z., McKean-Cowdin, R., Michaud, D. S., Wang, S. S., Bondy, M., Houlston, R., Jenkins, R. B., Wrensch, M., Yeager, M., Ahlbom, A., Albanes, D., Andersson, U., Freeman, L., Buring, J. E., Butler, M., Braganza, M., Carreon, T., Feychting, M., Fleming, S. J., Gapstur, S. M., Gaziano, J., Giles, G. G., Hallmans, G., Henriksson, R., Hoffman-Bolton, J., Inskip, P. D., Johansen, C., Kitahara, C. M., Lathrop, M., Liu, C., Le Marchand, L., Linet, M. S., Lonn, S., Peters, U., Purdue, M. P., Rothman, N., Ruder, A. M., Sanson, M., Sesso, H. D., Severi, G., Shu, X., Simon, M., Stampfer, M., Stevens, V. L., Visvanathan, K., White, E., Wolk, A., Zeleniuch-Jacquotte, A., Zheng, W., Decker, P., Enciso-Mora, V., Fridley, B., Gao, Y., Kosel, M., Lachance, D. H., Lau, C., Rice, T., Swerdlow, A., Wiemels, J. L., Wiencke, J. K., Shete, S., Xiang, Y., Xiao, Y., Hoover, R. N., Fraumeni, J. F., Chatterjee, N., Hartge, P., Chanock, S. J. 2012; 131 (12): 1877–88

    Abstract

    Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.

    View details for DOI 10.1007/s00439-012-1212-0

    View details for Web of Science ID 000310869700008

    View details for PubMedID 22886559

    View details for PubMedCentralID PMC3761216

  • Sitting time and health outcomes among Mexican origin adults: obesity as a mediator BMC PUBLIC HEALTH de Heer, H. D., Wilkinson, A. V., Strong, L. L., Bondy, M. L., Koehly, L. M. 2012; 12: 896

    Abstract

    Sitting time and sedentary behaviors have been associated with adverse health outcomes including obesity, diabetes and cardiovascular disease (CVD) within non- Hispanic White populations. Similar associations have not been described within Hispanic populations despite their high CVD risk profile. This study aimed to assess the association between sitting time and obesity, self-reported diagnosed diabetes, hypertension and high cholesterol among a large cohort (N=11,268) of Mexican origin adults and to assess whether obesity mediated these associations.Using a cross-sectional design, data collected between 2004 and 2010 were analyzed in late 2010. Regression analyses evaluated associations between self-reported daily sitting hours and disease outcomes, controlling for demographics, employment status, family disease history, and light, moderate and strenuous physical activity.Participants were mostly female (81.1%) Mexican origin adults. Sitting time was associated with increased odds of being obese, having diabetes and having hypertension, but not high cholesterol. Adjusted odds ratios of participants who reported sitting > 4 hours/day compared to those sitting 1-2 hours/day were for obesity OR=1.55 (95% CI 1.39, 1.73), p<.001, for diabetes OR=1.29 (95% CI, 1.09, 1.52), p=.003, for hypertension OR=1.17 (95% CI, 1.01, 1.37), p=.041. Associations controlled for physical activity and employment status. Effects on hypertension and diabetes were mediated by obesity.Sitting time was significantly associated with detrimental health outcomes, independent of physical activity. Obesity mediated these relationships for diabetes and hypertension. Future research should assess whether interventions addressing sitting time are feasible and effective among Mexican origin populations.

    View details for DOI 10.1186/1471-2458-12-896

    View details for Web of Science ID 000312744000001

    View details for PubMedID 23092387

    View details for PubMedCentralID PMC3527190

  • An exploratory case-only analysis of gene-hazardous air pollutant interactions and the risk of childhood medulloblastoma PEDIATRIC BLOOD & CANCER Lupo, P. J., Lee, L. J., Okcu, M., Bondy, M. L., Scheurer, M. E. 2012; 59 (4): 605–10

    Abstract

    There is evidence that exposure to chlorinated solvents may be associated with childhood medulloblastoma and primitive neuroectodermal tumor (M/PNET) risk. Animal models suggest genes related to detoxification and DNA repair are important in the carcinogenicity of these pollutants; however, there have been no human studies assessing the modifying effects of these genotypes on the association between chlorinated solvents and childhood M/PNET risk.We conducted a case-only study to evaluate census tract-level exposure to chlorinated solvents and the risk of childhood M/PNET in the context of detoxification and DNA repair genotypes. Cases (n = 98) were obtained from Texas Children's Hospital and MD Anderson Cancer Center. Key genotypes (n = 22) were selected from the Illumina Human 1M Quad SNP Chip. Exposure to chlorinated solvents (methylene chloride, perchloroethylene, trichloroethylene, and vinyl chloride) was estimated from the US EPA's 1999 Assessment System for Population Exposure Nationwide (ASPEN). Logistic regression was used to estimate the case-only odds ratios and 95% confidence intervals (CIs).There were 11 significant gene-environment interactions associated with childhood M/PNET risk. However, after correcting for multiple comparisons, only the interaction between high trichloroethylene levels and OGG1 rs293795 significantly increased the risk of childhood M/PNET risk (OR = 9.24, 95% CI: 2.24, 38.24, Q = 0.04).This study provides an initial assessment of the interaction between ambient levels of chlorinated solvents and potentially relevant genotypes on childhood M/PNET risk. Our results are exploratory and must be validated in animal models, as well as additional human studies.

    View details for DOI 10.1002/pbc.24105

    View details for Web of Science ID 000307386300003

    View details for PubMedID 22389292

    View details for PubMedCentralID PMC3371277

  • Dental x-rays and risk of meningioma CANCER Claus, E. B., Calvocoressi, L., Bondy, M. L., Schildkraut, J. M., Wiemels, J. L., Wrensch, M. 2012; 118 (18): 4530–37

    Abstract

    Ionizing radiation is a consistently identified and potentially modifiable risk factor for meningioma, which is the most frequently reported primary brain tumor in the United States. The objective of this study was to examine the association between dental x-rays-the most common artificial source of ionizing radiation-and the risk of intracranial meningioma.This population-based case-control study included 1433 patients who had intracranial meningioma diagnosed at ages 20 to 79 years and were residents of the states of Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area, and 8 counties in Houston, Texas between May 1, 2006 and April 28, 2011 (cases). A control group of 1350 individuals was frequency matched on age, sex, and geography (controls). The main outcome measure for the study was the association between a diagnosis of intracranial meningioma and self-reported bitewing, full-mouth, and panorex dental x-rays.Over a lifetime, cases were more than twice as likely as controls (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.4-2.9) to report having ever had a bitewing examination. Regardless of the age at which the films were obtained, individuals who reported receiving bitewing films on a yearly basis or with greater frequency had an elevated risk for ages <10 years (OR, 1.4; 95% CI, 1.0-1.8), ages 10 to 19 years (OR, 1.6; 95% CI, 1.2-2.0), ages 20 to 49 years (OR, 1.9; 95% CI, 1.4-2.6), and ages ≥40 years (OR, 1.5; 95% CI, 1.1-2.0). An increased risk of meningioma also was associated with panorex films taken at a young age or on a yearly basis or with greater frequency, and individuals who reported receiving such films at ages <10 years had a 4.9 times increased risk (95% CI, 1.8-13.2) of meningioma. No association was appreciated for tumor location above or below the tentorium.Exposure to some dental x-rays performed in the past, when radiation exposure was greater than in the current era, appears to be associated with an increased risk of intracranial meningioma. As with all sources of artificial ionizing radiation, considered use of this modifiable risk factor may be of benefit to patients.

    View details for DOI 10.1002/cncr.26625

    View details for Web of Science ID 000308404100024

    View details for PubMedID 22492363

    View details for PubMedCentralID PMC3396782

  • Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma HUMAN GENETICS Liu, Y., Melin, B. S., Rajaraman, P., Wang, Z., Linet, M., Shete, S., Amos, C. I., Lau, C. C., Scheurer, M. E., Tsavachidis, S., Armstrong, G. N., Houlston, R. S., Hosking, F. J., Claus, E. B., Barnholtz-Sloan, J., Lai, R., Il'yasova, D., Schildkraut, J., Sadetzki, S., Johansen, C., Bernstein, J. L., Olson, S. H., Jenkins, R. B., LaChance, D., Vick, N. A., Wrensch, M., Davis, F., McCarthy, B. J., Andersson, U., Thompson, P. A., Chanock, S., Bondy, M. L. 2012; 131 (9): 1507–17

    Abstract

    The risk of glioma has consistently been shown to be increased twofold in relatives of patients with primary brain tumors (PBT). A recent genome-wide linkage study of glioma families provided evidence for a disease locus on 17q12-21.32, with the possibility of four additional risk loci at 6p22.3, 12p13.33-12.1, 17q22-23.2, and 18q23. To identify the underlying genetic variants responsible for the linkage signals, we compared the genotype frequencies of 5,122 SNPs mapping to these five regions in 88 glioma cases with and 1,100 cases without a family history of PBT (discovery study). An additional series of 84 familial and 903 non-familial cases were used to replicate associations. In the discovery study, 12 SNPs showed significant associations with family history of PBT (P < 0.001). In the replication study, two of the 12 SNPs were confirmed: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.031) and 17q12-21.32 SPOP rs650461 (P = 0.025). In the combined analysis of discovery and replication studies, the strongest associations were attained at four SNPs: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.0001), SOX5 rs7305773 (P = 0.0001) and STKY1 rs2418087 (P = 0.0003), and 17q12-21.32 SPOP rs6504618 (P = 0.0006). Further, a significant gene-dosage effect was found for increased risk of family history of PBT with these four SNPs in the combined data set (P(trend) <1.0 × 10(-8)). The results support the linkage finding that some loci in the 12p13.33-12.1 and 17q12-q21.32 may contribute to gliomagenesis and suggest potential target genes underscoring linkage signals.

    View details for DOI 10.1007/s00439-012-1187-x

    View details for Web of Science ID 000307515600009

    View details for PubMedID 22688887

    View details for PubMedCentralID PMC3604903

  • Identification of germline genomic copy number variation in familial pancreatic cancer HUMAN GENETICS Al-Sukhni, W., Joe, S., Lionel, A. C., Zwingerman, N., Zogopoulos, G., Marshall, C. R., Borgida, A., Holter, S., Gropper, A., Moore, S., Bondy, M., Klein, A. P., Petersen, G. M., Rabe, K. G., Schwartz, A. G., Syngal, S., Scherer, S. W., Gallinger, S. 2012; 131 (9): 1481–94

    Abstract

    Adenocarcinoma of the pancreas is a significant cause of cancer mortality, and up to 10 % of cases appear to be familial. Heritable genomic copy number variants (CNVs) can modulate gene expression and predispose to disease. Here, we identify candidate predisposition genes for familial pancreatic cancer (FPC) by analyzing germline losses or gains present in one or more high-risk patients and absent in a large control group. A total of 120 FPC cases and 1,194 controls were genotyped on the Affymetrix 500K array, and 36 cases and 2,357 controls were genotyped on the Affymetrix 6.0 array. Detection of CNVs was performed by multiple computational algorithms and partially validated by quantitative PCR. We found no significant difference in the germline CNV profiles of cases and controls. A total of 93 non-redundant FPC-specific CNVs (53 losses and 40 gains) were identified in 50 cases, each CNV present in a single individual. FPC-specific CNVs overlapped the coding region of 88 RefSeq genes. Several of these genes have been reported to be differentially expressed and/or affected by copy number alterations in pancreatic adenocarcinoma. Further investigation in high-risk subjects may elucidate the role of one or more of these genes in genetic predisposition to pancreatic cancer.

    View details for DOI 10.1007/s00439-012-1183-1

    View details for Web of Science ID 000307515600007

    View details for PubMedID 22665139

    View details for PubMedCentralID PMC3808836

  • Gender Differences in Sociodemographic and Behavioral Influences of Physical Activity in Mexican-Origin Adolescents JOURNAL OF PHYSICAL ACTIVITY & HEALTH Strong, L. L., Anderson, C. B., Miranda, P. Y., Bondy, M. L., Zhou, R., Etzel, C., Spitz, M., Wilkinson, A. V. 2012; 9 (6): 829–39

    Abstract

    Understanding the factors that contribute to physical activity (PA) in Mexican-origin adolescents is essential to the design of effective efforts to enhance PA participation in this population.Multivariable logistic regression was used to identify sociodemographic and behavioral correlates of self-reported PA in school and community settings in 1154 Mexican-origin adolescents aged 12-17 years in Houston, TX.The majority of adolescents were born in the US (74%), approximately half (51%) were overweight or obese, and nearly three-quarters (73%) watched more than 2 hours of weekday television. Similarities and differences by setting and gender were observed in the relationships between sociodemographic and behavioral characteristics and PA. In boys, parental education and attending physical education (PE) were positively associated with PA across multiple PA outcomes. Adolescent linguistic acculturation was inversely associated with participation in community sports, whereas parental linguistic acculturation was positively associated with PA at school. In girls, PA in school and community settings was inversely associated with TV viewing and positively associated with PE participation.These findings highlight similarities and differences in correlates of PA among boys and girls, and point toward potential sources of opportunities as well as disparities for PA behaviors in Mexican-origin adolescents.

    View details for DOI 10.1123/jpah.9.6.829

    View details for Web of Science ID 000307747800009

    View details for PubMedID 21952224

    View details for PubMedCentralID PMC3250565

  • Higher Risk for Obesity Among Mexican-American and Mexican Immigrant Children and Adolescents than Among Peers in Mexico JOURNAL OF IMMIGRANT AND MINORITY HEALTH Hernandez-Valero, M. A., Patricia Bustamante-Montes, L., Hernandez, M., Halley-Castillo, E., Wilkinson, A. V., Bondy, M. L., Olvera, N. 2012; 14 (4): 517–22

    Abstract

    We conducted a cross-sectional study among 1,717 children and adolescents of Mexican origin ages 5-19 years living in Mexico and Texas to explore the influence of country of birth and country of longest residence on their overweight and obesity status. Descriptive statistics were used to compare demographic and anthropometric characteristics of participants born and raised in Mexico (Mexicans), born in Mexico and raised in the United States (Mexican immigrants), and born and raised in the United States (Mexican-Americans). Univariate and multivariate nominal logistic regression was used to determine the demographic predictors of obesity adjusted by country of birth, country of residence, age, and gender. Almost half (48.8%) of the Mexican-Americans and 43.2% of the Mexican immigrants had body mass index at the 85th percentile or above, compared to only 29.3% of the Mexicans (P < .001). Thus, Mexican-Americans and Mexican immigrants were more likely to be obese than their Mexican peers [Mexican-Americans: odds ratio (OR) = 2.5 (95% confidence interval [CI] 1.8-3.4); Mexican immigrants: OR = 2.2 (95% CI 1.6-3.0)]. In addition, males were more likely than females to be obese [OR = 1.6 (95% CI 1.2-2.1)], and adolescents 15-19 years of age were less likely than their younger counterparts [OR = 0.5 (95% CI 0.4-0.7)] to be obese. The high prevalence of obesity among children of Mexican origin in the United States is of great concern and underscores the urgent need to develop and implement obesity preventive interventions targeting younger children of Mexican origin, especially newly arrived immigrant children. In addition, future obesity research should take into consideration the country of origin of the study population to develop more culturally specific obesity interventions.

    View details for DOI 10.1007/s10903-011-9535-9

    View details for Web of Science ID 000305913600001

    View details for PubMedID 22002704

    View details for PubMedCentralID PMC5436600

  • Psychometric Evaluation of the Demographic Index of Cultural Exposure (DICE) in Two Mexican-Origin Community Samples HISPANIC JOURNAL OF BEHAVIORAL SCIENCES Cruz, R. A., Wilkinson, A. V., Bondy, M. L., Koehly, L. M. 2012; 34 (3): 404–20

    Abstract

    Reliability and validity evidence is provided for the Demographic Index of Cultural Exposure (DICE), consisting of six demographic proxy indicators of acculturation, within two community samples of Mexican-origin adults (N= 497 for each sample). Factor analytic procedures were used to examine the common variance shared between the six demographic indicators hypothesized to correlate with acculturation. The index was cross-validated across two samples by comparing fit indices. Finally, index criterion validity was assessed using correlations between index scores and five common behavioral/psychological domains of Latino cultural identity: language use (Spanish and English), cultural practices, folk health beliefs, and fatalism. Results indicated that the six demographic indicators loaded onto one latent factor and that this model had good fit across both samples. In addition, DICE scores correlated with four of the five behavioral/psychological measures. Future use of the DICE as an efficient way to approximate cultural exposure is discussed.

    View details for DOI 10.1177/0739986312449426

    View details for Web of Science ID 000306176500002

    View details for PubMedID 30498286

    View details for PubMedCentralID PMC6258078

  • Effect of gender on the production of autoantibodies to meningioma antigens Wiemels, J., Bracchi, P., Wrensch, M., Schildkraut, J., Bondy, M., Pfefferle, J., Zhou, M., Sison, J., Calvocoressi, L., Claus, E. B. SPRINGER HEIDELBERG. 2012: S45
  • Experimenting with cigarettes and physical activity among Mexican origin youth: a cross sectional analysis of the interdependent associations among sensation seeking, acculturation, and gender BMC PUBLIC HEALTH Wilkinson, A. V., Okeke, N. L., Springer, A. E., Stigler, M. H., Gabriel, K. P., Bondy, M. L., Prokhorov, A. V., Spitz, M. R. 2012; 12: 332

    Abstract

    Sensation seeking tendencies tend to manifest during adolescence and are associated with both health-compromising behaviors and health-enhancing behaviors. The purpose of this study is to evaluate the relationship between sensation seeking and physical activity, a health-enhancing behavior, and between sensation seeking and experimenting with cigarettes, a health compromising-behavior, among a cohort of Mexican origin adolescents residing in the United States with different levels of acculturation.In 2009, 1,154 Mexican origin youth (50.5% girls, mean age 14.3 years (SD = 1.04)) provided data on smoking behavior, physical activity, linguistic acculturation, and sensation seeking. We conducted Pearson's χ2 tests to examine the associations between categorical demographic characteristics (i.e. gender, age, country of birth and parental educational attainment) and both cigarette experimentation and physical activity and Student's t-tests to examine mean differences on the continuous variables (i.e. sensation seeking subscale) by the behaviors. We examined mean differences in the demographic characteristics, acculturation, and both behaviors for each of the sensation seeking subscales using analysis of variance (ANOVA). To examine relationships between the sensation seeking subscales, gender, and both behaviors, at different levels of acculturation we completed unconditional logistic regression analyses stratified by level of acculturation.Overall, 23.3% had experimented with cigarettes and 29.0% reported being physically active for at least 60 minutes/day on at least 5 days/week. Experimenting with cigarettes and being physically active were more prevalent among boys than girls. Among girls, higher levels of sensation seeking tendencies were associated with higher levels of acculturation and experimentation with cigarettes, but not with physical activity. Among boys, higher levels of sensation seeking tendencies were associated with higher levels of acculturation, experimenting with cigarettes and being physically active.Our results suggest that interventions designed to prevent smoking among Mexican origin youth may need to address social aspects associated with acculturation, paying close attention to gendered manifestations of sensation seeking.

    View details for DOI 10.1186/1471-2458-12-332

    View details for Web of Science ID 000308700200001

    View details for PubMedID 22559717

    View details for PubMedCentralID PMC3441442

  • Genetic variants in the vitamin D pathway and breast cancer disease free survival Pande, M., Thompson, P. A., Yoo, S., Doi, K., Sahin, A. A., Amos, C. I., Bondy, M., Brewster, A. AMER ASSOC CANCER RESEARCH. 2012
  • Genome-wide sequencing identifies ATM as a pancreatic cancer susceptibility gene Roberts, N. J., Jiao, Y., Yu, J., Kopelovich, L., Petersen, G. M., Bondy, M., Gallinger, S., Schwartz, A. G., Syngai, S., Cote, M. L., Axilbund, J., Schulick, R., Ali, S. Z., Eshleman, J. R., Velculescu, V., Goggins, M., Vogelstein, B., Papadopoulous, N., Hruban, R. H., Kinzler, K. W., Klein, A. P. AMER ASSOC CANCER RESEARCH. 2012
  • Maternal and offspring folate metabolic genes and the risk of childhood acute lymphoblastic leukemia (ALL) Lupo, P. J., Nousome, D., Kamdar, K. Y., Okcu, M. F., Bondy, M. L., Scheurer, M. E. AMER ASSOC CANCER RESEARCH. 2012
  • Dietary Intake, Physical activity and Overweight and Obesity in Mexican American Adolescents Zhu, Y., Hernandez, L., Dong, Y., Wilkinson, A., Strong, L., Bondy, M. L., Spitz, M. R., Forman, M. R. FEDERATION AMER SOC EXP BIOL. 2012
  • Gamma-ray-induced mutagen sensitivity and risk of sporadic breast cancer in young women: a case-control study BREAST CANCER RESEARCH AND TREATMENT Wang, L., Han, C. H., Xiong, P., Bondy, M. L., Yu, T., Brewster, A. M., Shete, S., Arun, B. K., Buchholz, T. A., Wei, Q. 2012; 132 (3): 1147–55

    Abstract

    Hypersensitivity to radiation exposure has been suggested to be a risk factor for the development of breast cancer. In this case-control study of 515 young women (≤ 55 years) with newly diagnosed sporadic breast cancer and 402 cancer-free controls, we examined the radiosensitivity as measured by the frequency of chromatid breaks induced by gamma-radiation exposure in the G2 phase of phytohemagglutinin-stimulated and short-term cultured fresh lymphocytes. We found that the average chromatid breaks per cell from 50 well-spread metaphases were statistically significantly higher in 403 non-Hispanic White breast cancer patients (0.52 ± 0.22) than that in 281 non-Hispanic White controls (0.44 ± 0.16) (P value < 0.001), and in 60 Mexican American breast cancer patients (0.52 ± 0.19) than that in 65 Mexican American controls (0.44 ± 0.16) (P value = 0.021), but the difference was not significant in African Americans (52 cases [0.45 ± 0.16] versus 56 controls [0.47 ± 0.16], P = 0.651). The frequency of chromatid breaks per cell above the median of control subjects was associated with two-fold increased risk for breast cancer in non-Hispanic Whites and Mexican Americans. A dose-response relationship was evident between radiosensitivity and risk for breast cancer (P (trend) < 0.001) in these two ethnic groups. We concluded that gamma-ray-induced mutagen sensitivity may play a role in susceptibility to breast cancer in young non-Hispanic White and Mexican American women.

    View details for DOI 10.1007/s10549-011-1940-1

    View details for Web of Science ID 000303379800037

    View details for PubMedID 22218884

    View details for PubMedCentralID PMC3523666

  • Primary Brain and Central Nervous System Neoplasms in the Automated Central Tumor Registry: 2000-2010 Theeler, B., Gilbert, M., Bondy, M. LIPPINCOTT WILLIAMS & WILKINS. 2012
  • Whole-Genome Detection of Deletions Associated with Glioma in a Case-Control Study Using SNPs Wu, C., Yu, R., Ma, L., Armstrong, G., Liu, Y., Lau, C., Bondy, M., Shete, S. WILEY-BLACKWELL. 2012: 154
  • A Review of Cancer in US Hispanic Populations CANCER PREVENTION RESEARCH Haile, R. W., John, E. M., Levine, A. J., Cortessis, V. K., Unger, J. B., Gonzales, M., Ziv, E., Thompson, P., Spruijt-Metz, D., Tucker, K. L., Bernstein, J. L., Rohan, T. E., Ho, G. Y., Bondy, M. L., Martinez, M. E., Cook, L., Stern, M. C., Correa, M. C., Wright, J., Schwartz, S. J., Baezconde-Garbanati, L., Blinder, V., Miranda, P., Hayes, R., Friedman-Jimenez, G., Monroe, K. R., Haiman, C. A., Henderson, B. E., Thomas, D. C., Boffetta, P. 2012; 5 (2): 150-163

    Abstract

    There are compelling reasons to conduct studies of cancer in Hispanics, the fastest growing major demographic group in the United States (from 15% to 30% of the U.S. population by 2050). The genetically admixed Hispanic population coupled with secular trends in environmental exposures and lifestyle/behavioral practices that are associated with immigration and acculturation offer opportunities for elucidating the effects of genetics, environment, and lifestyle on cancer risk and identifying novel risk factors. For example, traditional breast cancer risk factors explain less of the breast cancer risk in Hispanics than in non-Hispanic whites (NHW), and there is a substantially greater proportion of never-smokers with lung cancer in Hispanics than in NHW. Hispanics have higher incidence rates for cancers of the cervix, stomach, liver, and gall bladder than NHW. With respect to these cancers, there are intriguing patterns that warrant study (e.g., depending on country of origin, the five-fold difference in gastric cancer rates for Hispanic men but not Hispanic women). Also, despite a substantially higher incidence rate and increasing secular trend for liver cancer in Hispanics, there have been no studies of Hispanics reported to date. We review the literature and discuss study design options and features that should be considered in future studies.

    View details for DOI 10.1158/1940-6207.CAPR-11-0447

    View details for Web of Science ID 000300043500002

    View details for PubMedID 22307564

  • Cigarette Experimentation in Mexican Origin Youth: Psychosocial and Genetic Determinants CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Wilkinson, A. V., Bondy, M. L., Wu, X., Wang, J., Dong, Q., D'Amelio, A. M., Prokhorov, A. V., Pu, X., Yu, R. K., Etzel, C. J., Shete, S., Spitz, M. R. 2012; 21 (1): 228–38

    Abstract

    Established psychosocial risk factors increase the risk for experimentation among Mexican origin youth. Now, we comprehensively investigate the added contribution of select polymorphisms in candidate genetic pathways associated with sensation seeking, risk taking, and smoking phenotypes to predict experimentation.Participants (N = 1,118 Mexican origin youth) recruited from a large population-based cohort study in Houston, TX, provided prospective data on cigarette experimentation over 3 years. Psychosocial data were elicited twice-baseline and final follow-up. Participants were genotyped for 672 functional and tagging variants in the dopamine, serotonin, and opioid pathways.After adjusting for gender and age, with a Bayesian False Discovery Probability set at 0.8 and prior probability of 0.05, six gene variants were significantly associated with risk of experimentation. After controlling for established risk factors, multivariable analyses revealed that participants with six or more risk alleles were 2.25 [95% confidence interval (CI), 1.62-3.13] times more likely to have experimented since baseline than participants with five or fewer. Among committed never-smokers (N = 872), three genes (OPRM1, SNAP25, HTR1B) were associated with experimentation as were all psychosocial factors. Among susceptible youth (N = 246), older age at baseline, living with a smoker, and three different genes (HTR2A, DRD2, SLC6A3) predicted experimentation.Our findings, which have implications for development of culturally specific interventions, need to be validated in other ethnic groups.These results suggest that variations in select genes interact with a cognitive predisposition toward smoking. In susceptible adolescents, the impact of the genetic variants appears to be larger than committed never-smokers.

    View details for DOI 10.1158/1055-9965.EPI-11-0456

    View details for Web of Science ID 000299051500024

    View details for PubMedID 22028400

    View details for PubMedCentralID PMC3382046

  • Factors that influence mammography use and breast cancer detection among Mexican-American and African-American women CANCER CAUSES & CONTROL Garcia, R., Carvajal, S. C., Wilkinson, A. V., Thompson, P. A., Nodora, J. N., Komenaka, I. K., Brewster, A., Cruz, G. I., Wertheim, B. C., Bondy, M. L., Martinez, M. 2012; 23 (1): 165–73

    Abstract

    This study examined factors that influence mammography use and breast cancer detection, including education, health insurance, and acculturation, among Mexican-American (MA) and African-American (AA) women.The study included 670 breast cancer cases (388 MAs and 282 AAs), aged 40-86 years at diagnosis. Data on mammography use, detection, and delay in seeking care were collected via questionnaires and medical records. Using a language-based bidimensional acculturation measure, MAs were classified as English-dominant (n = 67), bilingual (n = 173), and Spanish-dominant (n = 148). Mammography prior to diagnosis was assessed by racial/ethnic acculturation subgroup using logistic regression.In age-adjusted models, mammography use was non-significantly lower among English-dominant (OR = 0.84; 95% CI: 0.45-1.59) and bilingual (OR = 0.86; 95% CI: 0.55-1.35) MAs and significantly lower among Spanish-dominant MAs (OR = 0.53; 95% CI: 0.34-0.83) than among AA women. After adjustment for education or insurance, there was no difference in mammography use by race/ethnicity and acculturation subgroup. Despite high self-reported mammography use (75%), a large proportion of cases reported self-detection (59%) and delay in seeking care >90 days (17%).These findings favor promoting culturally appropriate messaging about the benefits and limitations of mammography, education about breast awareness, and prompt reporting of findings to a health professional.

    View details for DOI 10.1007/s10552-011-9865-x

    View details for Web of Science ID 000297757400016

    View details for PubMedID 22080276

    View details for PubMedCentralID PMC6684027

  • Cytoplasmic Cyclin E and P-CDK2 Expression in Triple Negative Breast Carcinomas Measured by Immunohistochemistry Correlates with Poor Outcome. Biernacka, A., Karakas, C., Wingate, H., Bondy, M., Sahin, A., Hunt, K., Khandan, K. AMER ASSOC CANCER RESEARCH. 2011
  • Genome-Wide High-Density SNP Linkage Search for Glioma Susceptibility Loci: Results from the Gliogene Consortium CANCER RESEARCH Shete, S., Lau, C. C., Houlston, R. S., Claus, E. B., Barnholtz-Sloan, J., Lai, R., Il'yasova, D., Schildkraut, J., Sadetzki, S., Johansen, C., Bernstein, J. L., Olson, S. H., Jenkins, R. B., Yang, P., Vick, N. A., Wrensch, M., Davis, F. G., McCarthy, B. J., Leung, E., Davis, C., Cheng, R., Hosking, F. J., Armstrong, G. N., Liu, Y., Yu, R. K., Henriksson, R., Melin, B. S., Bondy, M. L., Gliogene Consortium 2011; 71 (24): 7568–75

    Abstract

    Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have shown that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium single-nucleotide polymorphism, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P = 0.0005) at 17q12-21.32 and the Z-score of 4.20 (P = 0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P = 0.008) and the Z-score of 1.47 (P = 0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P = 0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susceptibility, focusing future work to identify genes that cause familial glioma.

    View details for DOI 10.1158/0008-5472.CAN-11-0013

    View details for Web of Science ID 000298407900024

    View details for PubMedID 22037877

    View details for PubMedCentralID PMC3242820

  • Triple-Negative Subtype Predicts Poor Overall Survival and High Locoregional Relapse in Inflammatory Breast Cancer ONCOLOGIST Li, J., Gonzalez-Angulo, A. M., Allen, P. K., Yu, T. K., Woodward, W. A., Ueno, N. T., Lucci, A., Krishnamurthy, S., Gong, Y., Bondy, M. L., Yang, W., Willey, J. S., Cristofanilli, M., Valero, V., Buchholz, T. A. 2011; 16 (12): 1675–83

    Abstract

    Numerous studies have demonstrated that expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2 is important for predicting overall survival (OS), distant relapse (DR), and locoregional relapse (LRR) in early and advanced breast cancer patients. However, these findings have not been confirmed for inflammatory breast cancer (IBC), which has different biological features than non-IBC.We retrospectively analyzed the records of 316 women who presented to MD Anderson Cancer Center in 1989-2008 with newly diagnosed IBC without distant metastases. Most patients received neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Patients were grouped according to receptor status: ER(+) (ER(+)/PR(+) and HER-2-; n = 105), ER(+)HER-2(+) (ER(+)/PR(+) and HER-2(+); n = 37), HER-2(+) (ER(-)/PR(-) and HER-2(+); n = 83), or triple-negative (TN) (ER(-)PR(-)HER-2(-); n = 91). Kaplan-Meier and Cox proportional hazards methods were used to assess LRR, DR, and OS rates and their associations with prognostic factors.The median age was 50 years (range, 24-83 years). The median follow-up time and median OS time for all patients were both 33 months. The 5-year actuarial OS rates were 58.7% for the entire cohort, 69.7% for ER(+) patients, 73.5% for ER(+)HER-2(+) patients, 54.0% for HER=2(+) patients, and 42.7% for TN patients (p < .0001); 5-year LRR rates were 20.3%, 8.0%, 12.6%, 22.6%, and 38.6%, respectively, for the four subgroups (p < .0001); and 5-year DR rates were 45.5%, 28.8%, 50.1%, 52.1%, and 56.7%, respectively (p < .001). OS and LRR rates were worse for TN patients than for any other subgroup (p < .0001-.03).TN disease is associated with worse OS, DR, and LRR outcomes in IBC patients, indicating the need for developing new locoregional and systemic treatment strategies for patients with this aggressive subtype.

    View details for DOI 10.1634/theoncologist.2011-0196

    View details for Web of Science ID 000298661000005

    View details for PubMedID 22147002

    View details for PubMedCentralID PMC3248766

  • A review of body size and breast cancer risk in Hispanic and African American women CANCER Sexton, K. R., Franzini, L., Day, R., Brewster, A., Vernon, S. W., Bondy, M. L. 2011; 117 (23): 5271–81

    Abstract

    Obesity is an epidemic in the United States, especially among Hispanics and African Americans. Studies of obesity and breast cancer risk have been conducted primarily in non-Hispanic whites. There have been few studies of the association between body mass index (BMI) or weight gain and the risk of breast cancer in minorities, and the results have been inconsistent. Because most studies are conducted primarily in non-Hispanic whites, the etiology of breast cancer in minorities is not well understood. The authors of the current report reviewed the literature on the association between obesity, weight, and weight gain and breast cancer in minorities using a combination of the Medical Subject Heading (MeSH) terms "obesity," "body mass index," "weight," "weight gain," "Hispanic," and "African American." Only publications in English and with both risk estimates and 95% confidence intervals were considered. Forty-five studies of body size and breast cancer risk in non-Hispanic whites were identified. After an exhaustive search of the literature, only 3 studies of body size and breast cancer were conducted in Hispanic women were identified, and only 8 such studies in African American women were identified. The results were inconsistent in both race/ethnicity groups, with studies reporting positive, inverse, and null results. Thus, as obesity rates among Hispanics and African Americans continue to rise, there is an urgent need to identify the roles that both obesity and adult weight gain play in the development of breast cancer in these minorities. Additional studies are needed to provide more understanding of the etiology of this disease and to explain some of the disparities in incidence and mortality.

    View details for DOI 10.1002/cncr.26217

    View details for Web of Science ID 000297161000006

    View details for PubMedID 21598244

  • Family and personal medical history and risk of meningioma Clinical article JOURNAL OF NEUROSURGERY Claus, E. B., Calvocoressi, L., Bondy, M. L., Schildkraut, J. M., Wiemels, J. L., Wrensch, M. 2011; 115 (6): 1072–77

    Abstract

    Little is known about the epidemiology of meningioma, the most frequently reported primary brain tumor in the US. The authors undertook a case-control study to examine the relationship between family and personal medical history and meningioma risk.The authors compared the personal and first-degree family histories of 1124 patients with meningioma (age range 20-79 years) in Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area, and 8 Houston counties between May 1, 2006, and February 26, 2010, and the histories of 1000 control individuals who were frequency-matched for age, sex, and geography.The patients were more likely than the controls to report a first-degree family history of meningioma (OR 4.4, 95% CI 1.6-11.5), and there was an even stronger association in younger cases. The patients were less likely than controls to report immune conditions including allergy (OR 0.6, 95% CI 0.5-0.7) but were more likely to report a history of thyroid cancer (OR 4.7, 95% CI 1.02-21.5) or leukemia (OR 5.4, 95% CI 1.2-24.1) (most after radiotherapy). Among women, patients were more likely than controls to report hormonally related conditions--uterine fibroid tumors (OR 1.2, 95% CI 1.0-1.5), endometriosis (OR 1.5, 95% CI 1.5-2.1), and breast cancer (OR 1.4, 95% CI 0.8-2.3).The influence of genetics, the immune system, and radiation near the head on meningioma risk is suggested in the authors' findings; the role of hormones is intriguing but requires further study.

    View details for DOI 10.3171/2011.6.JNS11129

    View details for Web of Science ID 000297450700003

    View details for PubMedID 21780859

    View details for PubMedCentralID PMC3241000

  • Effects of antihistamine and anti-inflammatory medication use on risk of specific glioma histologies INTERNATIONAL JOURNAL OF CANCER Scheurer, M. E., Amirian, E., Davlin, S. L., Rice, T., Wrensch, M., Bondy, M. L. 2011; 129 (9): 2290–96

    Abstract

    Several studies have shown a decrease in glioma risk associated with a personal history of allergic conditions and the medications used to treat the symptoms. However, few studies have been able to examine risk within histological subgroups of glioma. Case-control data from M. D. Anderson Cancer Center and University of California, San Francisco were pooled to conduct the analysis stratified by histological subtype. A risk prediction model considering inflammation-related variables and antihistamine use was built using logistic regression. Of the subtypes examined, long-term antihistamine use was associated with increased risk of anaplastic gliomas, especially when length of use was considered in conjunction with history of asthma or allergy. Anaplastic cases with no history of asthma or allergy were 2.94 times more likely than controls to report antihistamine use for 10 years or more; whereas anaplastic cases with a history of asthma or allergy were 2.34 times more likely than controls to report antihistamine use for 10 years or more. Furthermore, anti-inflammatory medication use was associated with a protective effect against glioblastoma (OR = 0.80; 95% CI: 0.65, 0.99), especially among individuals with no history of asthma or allergies. No statistically significant effects of anti-inflammatory drugs or antihistamines were evident for the other histological subtypes. Thus, modulation of the immune system by the use of common drugs, such as antihistamines or nonsteroidal anti-inflammatory drugs, may contribute to the development of certain types of brain tumors.

    View details for DOI 10.1002/ijc.25883

    View details for Web of Science ID 000295230500024

    View details for PubMedID 21190193

    View details for PubMedCentralID PMC3125483

  • INTERLEUKIN-4 RECEPTOR ALPHA CHAIN (IL-4R-ALPHA) PROMOTES THE IMMUNOSUPPRESSIVE ACTIVITY OF GLIOMA-INFILTRATING MONOCYTES Kohanbash, G., McKaveney, K., Sakaki, M., Mintz, A., Ohlfest, J., Bondy, M., Fujita, M., Okada, H. OXFORD UNIV PRESS INC. 2011: 31
  • ELK-1 REGULATES INTERFERON-ALPHA-8 EXPRESSION VIA A POLYMORPHIC REGION IN INTERFERON-ALPHA-8 PROMOTER ASSOCIATED WITH THE PROGNOSIS OF GLIOMA PATIENTS Kohanbash, G., Ishikawa, E., Fujita, M., Ohno, M., Liu, Y., Sakaki, M., Ikeura, M., Scheurer, M., Bondy, M., Okada, H. OXFORD UNIV PRESS INC. 2011: 32
  • Reduced allergy and immunoglobulin E among adults with intracranial meningioma compared to controls INTERNATIONAL JOURNAL OF CANCER Wiemels, J. L., Wrensch, M., Sison, J. D., Zhou, M., Bondy, M., Calvocoressi, L., Black, P. M., Yu, H., Schildkraut, J. M., Claus, E. B. 2011; 129 (8): 1932–39

    Abstract

    Meningioma, the most frequent tumor in the central nervous system, has few recognized risk factors. We explored the role of allergies in a population-based case-control consortium study of meningioma in five geographic areas. We also studied serum levels of a marker of atopic allergy (IgE) in a subset of study participants, a first for a study on meningioma. Participants (N = 1,065) with surgically resected, pathologically confirmed meningioma and controls (N = 634) selected via random-digit dialing were recruited and interviewed. Cases were less likely than controls to report history of physician-diagnosed allergy [odds ratio (OR) = 0.64; 95% confidence interval (95% CI): 0.51-0.80]. Also, cases (N = 295) had lower total serum IgE than controls [N = 192; OR = 0.85, 95% CI: 0.75-0.98 for each unit of Ln(IgE)]. Similar to glioma and cancers at several other sites, meningioma appears to have an inverse relationship with history of allergies and a biomarker of atopic allergy. As some common opposing predisposition or developmental processes for allergy and meningioma may exist, further research into immune processes that can affect the incidence and natural history of meningioma is warranted.

    View details for DOI 10.1002/ijc.25858

    View details for Web of Science ID 000294224300015

    View details for PubMedID 21520030

    View details for PubMedCentralID PMC3337969

  • Copy Number Imbalances between Screen- and Symptom-Detected Breast Cancers and Impact on Disease-Free Survival CANCER PREVENTION RESEARCH Brewster, A. M., Thompson, P., Sahin, A. A., Do, K., Edgerton, M., Murray, J. L., Tsavachidis, S., Zhou, R., Liu, Y., Zhang, L., Mills, G., Bondy, M. 2011; 4 (10): 1609–16

    Abstract

    Screening mammography results in the increased detection of indolent tumors. We hypothesized that screen- and symptom-detected tumors would show genotypic differences as copy number imbalances (CNI) that, in part, explain differences in the clinical behavior between screen- and symptom-detected breast tumors. We evaluated 850 women aged 40 and above diagnosed with stage I and II breast cancer at the University of Texas MD Anderson Cancer Center between 1985 and 2000 with information available on method of tumor detection (screen vs. symptoms). CNIs in screen- and symptom-detected tumors were identified using high-density molecular inversion probe arrays. Cox proportional modeling was used to estimate the effect of method of tumor detection on disease-free survival after adjusting for age, stage, and the CNIs. The majority of tumors were symptom detected (n = 603) compared with screen detected (n = 247). Copy number gains in chromosomes 2p, 3q, 8q, 11p, and 20q were associated with method of breast cancer detection (P < 0.00001). We estimated that 32% and 63% of the survival advantage of screen detection was accounted for by age, stage, nuclear grade, and Ki67 in women aged 50 to 70 and aged 40 to 87, respectively. In each age category, an additional 20% of the survival advantage was accounted for by CNIs associated with method of detection. Specific CNIs differ between screen- and symptom-detected tumors and explain part of the survival advantage associated with screen-detected tumors. Measurement of tumor genotype has the potential to improve discrimination between indolent and aggressive screen-detected tumors and aids patient and physician decision making about use of surgical and adjuvant treatments.

    View details for DOI 10.1158/1940-6207.CAPR-10-0361

    View details for Web of Science ID 000295620000013

    View details for PubMedID 21795423

    View details for PubMedCentralID PMC3188338

  • Folate Pathway Polymorphisms Predict Deficits in Attention and Processing Speed After Childhood Leukemia Therapy PEDIATRIC BLOOD & CANCER Kamdar, K. Y., Krull, K. R., El-Zein, R. A., Brouwers, P., Potter, B. S., Harris, L. L., Holm, S., Dreyer, Z., Scaglia, F., Etzel, C. J., Bondy, M., Okcu, M. 2011; 57 (3): 454–60

    Abstract

    Neurocognitive impairment occurs in 20-40% of childhood acute lymphoblastic leukemia (ALL) survivors, possibly mediated by folate depletion and homocysteine elevation following methotrexate treatment. We evaluated the relationship between folate pathway polymorphisms and neurocognitive impairment after childhood ALL chemotherapy.Seventy-two childhood ALL survivors treated with chemotherapy alone underwent a neurocognitive battery consisting of: Trail Making Tests A (TMTA) and B (TMTB), Grooved Pegboard Test Dominant-Hand and Nondominant-Hand, Digit Span subtest, and Verbal Fluency Test. We performed genotyping for: 10-methylenetetrahydrofolate reductase (MTHFR 677C>T and MTHFR 1298A>C), serine hydroxymethyltransferase (SHMT 1420C>T), methionine synthase (MS 2756 A>G), methionine synthase reductase (MTRR 66A>G), and thymidylate synthase (TSER). Student's two sample t-test and analysis of covariance were used to compare test scores by genotype.General impairment on the neurocognitive battery was related to MTHFR 1298A>C (P = 0.03) and MS 2756A>G (P = 0.05). Specifically, survivors with MTHFR 1298AC/CC genotypes scored, on average, 13 points lower on TMTB than those with MTHFR 1298AA genotype (P = 0.001). The MS 2756AA genotype was associated with a 12.2 point lower mean TMTA score, compared to MS 2756 AG/GG genotypes (P = 0.01). The TSER 2R/3R and 3R/3R genotypes were associated with an 11.4 point lower mean score on TMTB, compared to the TSER 2R/2R genotype (P = 0.03). Survivors with ≥6 folate pathway risk alleles demonstrated a 9.5 point lower mean TMTA score (P = 0.06) and 14.5 point lower TMTB score (P = 0.002) than survivors with <6 risk alleles.Folate pathway polymorphisms are associated with deficits in attention and processing speed after childhood ALL therapy.

    View details for DOI 10.1002/pbc.23162

    View details for Web of Science ID 000293272800016

    View details for PubMedID 21618410

    View details for PubMedCentralID PMC3134130

  • Genetic variations in VEGF and VEGFR2 and glioblastoma outcome JOURNAL OF NEURO-ONCOLOGY Sjostrom, S., Wibom, C., Andersson, U., Brannstrom, T., Broholm, H., Johansen, C., Collatz-Laier, H., Liu, Y., Bondy, M., Henriksson, R., Melin, B. 2011; 104 (2): 523–27

    Abstract

    Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) are central components in the development and progression of glioblastoma. To investigate if genetic variation in VEGF and VEGFR2 is associated with glioblastoma prognosis, we examined blood samples from 154 glioblastoma cases collected in Sweden and Denmark between 2000 and 2004. Seventeen tagging single nucleotide polymorphisms (SNPs) in VEGF and 27 in VEGFR2 were genotyped and analysed, covering 90% of the genetic variability within the genes. In VEGF, we found no SNPs associated with survival. In VEGFR2, we found two SNPs significantly associated to survival, namely rs2071559 and rs12502008. However, these results are likely to be false positives due to multiple testing and could not be confirmed in a separate dataset. Overall, this study provides little evidence that VEGF and VEGFR2 polymorphisms are important for glioblastoma survival.

    View details for DOI 10.1007/s11060-010-0504-2

    View details for Web of Science ID 000294263800011

    View details for PubMedID 21191630

    View details for PubMedCentralID PMC3161189

  • Selective Genomic Copy Number Imbalances and Probability of Recurrence in Early-Stage Breast Cancer PLOS ONE Thompson, P. A., Brewster, A. M., Do, K., Baladandayuthapani, V., Broom, B. M., Edgerton, M. E., Hahn, K. M., Murray, J. L., Sahin, A., Tsavachidis, S., Wang, Y., Zhang, L., Hortobagyi, G. N., Mills, G. B., Bondy, M. L. 2011; 6 (8): e23543

    Abstract

    A number of studies of copy number imbalances (CNIs) in breast tumors support associations between individual CNIs and patient outcomes. However, no pattern or signature of CNIs has emerged for clinical use. We determined copy number (CN) gains and losses using high-density molecular inversion probe (MIP) arrays for 971 stage I/II breast tumors and applied a boosting strategy to fit hazards models for CN and recurrence, treating chromosomal segments in a dose-specific fashion (-1 [loss], 0 [no change] and +1 [gain]). The concordance index (C-Index) was used to compare prognostic accuracy between a training (n = 728) and test (n = 243) set and across models. Twelve novel prognostic CNIs were identified: losses at 1p12, 12q13.13, 13q12.3, 22q11, and Xp21, and gains at 2p11.1, 3q13.12, 10p11.21, 10q23.1, 11p15, 14q13.2-q13.3, and 17q21.33. In addition, seven CNIs previously implicated as prognostic markers were selected: losses at 8p22 and 16p11.2 and gains at 10p13, 11q13.5, 12p13, 20q13, and Xq28. For all breast cancers combined, the final full model including 19 CNIs, clinical covariates, and tumor marker-approximated subtypes (estrogen receptor [ER], progesterone receptor, ERBB2 amplification, and Ki67) significantly outperformed a model containing only clinical covariates and tumor subtypes (C-Index(full model), train[test]  =  0.72[0.71] ± 0.02 vs. C-Index(clinical + subtype model), train[test]  =  0.62[0.62] ± 0.02; p<10(-6)). In addition, the full model containing 19 CNIs significantly improved prognostication separately for ER-, HER2+, luminal B, and triple negative tumors over clinical variables alone. In summary, we show that a set of 19 CNIs discriminates risk of recurrence among early-stage breast tumors, independent of ER status. Further, our data suggest the presence of specific CNIs that promote and, in some cases, limit tumor spread.

    View details for DOI 10.1371/journal.pone.0023543

    View details for Web of Science ID 000293953500053

    View details for PubMedID 21858162

    View details for PubMedCentralID PMC3155554

  • A Novel Approach to Exploring Potential Interactions among Single-Nucleotide Polymorphisms of Inflammation Genes in Gliomagenesis: An Exploratory Case-Only Study CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Amirian, E., Scheurer, M. E., Liu, Y., D'Amelio, A. M., Houlston, R. S., Etzel, C. J., Shete, S., Swerdlow, A. J., Schoemaker, M. J., McKinney, P. A., Fleming, S. J., Muir, K. R., Lophatananon, A., Bondy, M. L. 2011; 20 (8): 1683–89

    Abstract

    Despite extensive research on the topic, glioma etiology remains largely unknown. Exploration of potential interactions between single-nucleotide polymorphisms (SNP) of immune genes is a promising new area of glioma research. The case-only study design is a powerful and efficient design for exploring possible multiplicative interactions between factors that are independent of one another. The purpose of our study was to use this exploratory design to identify potential pair wise SNP-SNP interactions from genes involved in several different immune-related pathways for investigation in future studies.The study population consisted of two case groups: 1,224 histologic confirmed, non-Hispanic white glioma cases from the United States and a validation population of 634 glioma cases from the United Kingdom. Polytomous logistic regression, in which one SNP was coded as the outcome and the other SNP was included as the exposure, was utilized to calculate the ORs of the likelihood of cases simultaneously having the variant alleles of two different SNPs. Potential interactions were examined only between SNPs located in different genes or chromosomes.Using this data mining strategy, we found 396 significant SNP-SNP interactions among polymorphisms of immune-related genes that were present in both the U.S. and U.K. study populations.This exploratory study was conducted for the purpose of hypothesis generation, and thus has provided several new hypotheses that can be tested using traditional case-control study designs to obtain estimates of risk.This is the first study, to our knowledge, to take this novel approach to identifying SNP-SNP interactions relevant to glioma etiology.

    View details for DOI 10.1158/1055-9965.EPI-11-0203

    View details for Web of Science ID 000293625600013

    View details for PubMedID 21724854

    View details for PubMedCentralID PMC3904785

  • Chromosome 7p11.2 (EGFR) variation influences glioma risk HUMAN MOLECULAR GENETICS Sanson, M., Hosking, F. J., Shete, S., Zelenika, D., Dobbins, S. E., Ma, Y., Enciso-Mora, V., Idbaih, A., Delattre, J., Hoang-Xuan, K., Marie, Y., Boisselier, B., Carpentier, C., Wang, X., Di Stefano, A., Labussiere, M., Gousias, K., Schramm, J., Boland, A., Lechner, D., Gut, I., Armstrong, G., Liu, Y., Yu, R., Lau, C., Di Bernardo, M., Robertson, L. B., Muir, K., Hepworth, S., Swerdlow, A., Schoemaker, M. J., Wichmann, H., Mueller, M., Schreiber, S., Franke, A., Moebus, S., Eisele, L., Foersti, A., Hemminki, K., Lathrop, M., Bondy, M., Houlston, R. S., Simon, M. 2011; 20 (14): 2897–2904

    Abstract

    While gliomas are the most common primary brain tumors, their etiology is largely unknown. To identify novel risk loci for glioma, we conducted genome-wide association (GWA) analysis of two case-control series from France and Germany (2269 cases and 2500 controls). Pooling these data with previously reported UK and US GWA studies provided data on 4147 glioma cases and 7435 controls genotyped for 424 460 common tagging single-nucleotide polymorphisms. Using these data, we demonstrate two statistically independent associations between glioma and rs11979158 and rs2252586, at 7p11.2 which encompasses the EGFR gene (population-corrected statistics, P(c) = 7.72 × 10(-8) and 2.09 × 10(-8), respectively). Both associations were independent of tumor subtype, and were independent of EGFR amplification, p16INK4a deletion and IDH1 mutation status in tumors; compatible with driver effects of the variants on glioma development. These findings show that variation in 7p11.2 is a determinant of inherited glioma risk.

    View details for DOI 10.1093/hmg/ddr192

    View details for Web of Science ID 000292560300018

    View details for PubMedID 21531791

    View details for PubMedCentralID PMC3118762

  • ASSOCIATION BETWEEN LEPTIN CONCENTRATION AND OBESITY IN MEXICAN-AMERICAN WOMEN WITH BREAST CANCER Sexton, T., Avery, A., El-Zein, B. R., Bondy, M. L. OXFORD UNIV PRESS INC. 2011: S91
  • Associations between Vaccination and Childhood Cancers in Texas Regions JOURNAL OF PEDIATRICS Pagaoa, M. A., Okcu, M., Bondy, M. L., Scheurer, M. E. 2011; 158 (6): 996–1002

    Abstract

    To determine whether children born in Texas regions with higher vaccination coverage had reduced risk of childhood cancer.The Texas Cancer Registry identified 2800 cases diagnosed from 1995 to 2006 who were (1) born in Texas and (2) diagnosed at ages 2 to 17 years. The state birth certificate data were used to identify 11 200 age- and sex-matched control subjects. A multilevel mixed-effects regression model compared vaccination rates among cases and control subjects at the public health region and county level.Children born in counties with higher hepatitis B vaccine coverage had lower odds of all cancers combined (OR = 0.81, 95% CI: 0.67 to 0.98) and acute lymphoblastic leukemia (ALL) specifically (OR = 0.63, 95% CI: 0.46 to 0.88). A decreased odds for ALL also was associated at the county level with higher rates of the inactivated poliovirus vaccine (OR = 0.67, 95% CI: 0.49 to 0.92) and 4-3-1-3-3 vaccination series (OR = 0.62, 95% CI: 0.44 to 0.87). Children born in public health regions with higher coverage levels of the Haemophilus influenzae type b-conjugate vaccine had lower odds of ALL (OR: 0.58; 95% CI: 0.42 to 0.82).Some common childhood vaccines appear to be protective against ALL at the population level.

    View details for DOI 10.1016/j.jpeds.2010.11.054

    View details for Web of Science ID 000290558600027

    View details for PubMedID 21227448

    View details for PubMedCentralID PMC6448142

  • Racial variation of leptin levels in women with breast cancer Avery, T. P., Sexton, K. R., Brewster, A., El-Zein, R., Bondy, M. AMER SOC CLINICAL ONCOLOGY. 2011
  • Prognostic value of single nucleotide polymorphisms (SNPs) of candidate genes associated with inflammation in early-stage Murray, J. L., Thompson, P., Zhou, R., Yoo, S. Y., Liu, Y., Do, K., Sahin, A. A., Bondy, M., Brewster, A. M. AMER SOC CLINICAL ONCOLOGY. 2011
  • Predictors of direct costs of diabetes care in pediatric patients with type 1 diabetes PEDIATRIC DIABETES Ying, A. K., Lairson, D. R., Giardino, A. P., Bondy, M. L., Zaheer, I., Haymond, M. W., Heptulla, R. A. 2011; 12 (3): 177–82

    Abstract

    This study examines factors that predict elevated direct costs of pediatric patients with type 1 diabetes.A cohort of 784 children with type 1 diabetes at least 6 months postdiagnosis and managed by pediatric endocrinologists at Texas Children's Hospital were included in this study. Actual reimbursed costs from January 2004 to December 2005 were obtained. Medication and supply costs were based on estimates from insulin dosage and type of insulin regimen prescribed, respectively. We examined utilization of care, total diabetes-related direct medical costs, and predictors of direct costs and hospitalization.Annually, 7% (58/784) of patients (excluding initial hospitalization at diagnosis) had a diabetes-related hospitalization and median length of stay was days. Mean total diabetes-related direct cost per person-year was $4730 [95% confidence interval (CI), 4516-4944]. Supplies accounted for 38% and medications 33% of costs, respectively. Older age, hemoglobin A(1C) (HbA(1C) ) > 8.5%, use of a multi-injection or pump regimen, living in a non-married household, and female gender were associated with higher annual costs. HbA(1C) > 8.5%, living in a non-married household, and female gender increased the odds of a diabetes-related hospitalization.Better metabolic control in patients with type 1 diabetes was associated with lower direct medical costs and lower odds of hospitalization. Marital status of the primary caregiver, irrespective of type of insurance, impacts the patient's healthcare costs and risk of hospitalization. This large single-center US study analyzes cost distribution in children with diabetes and is informative for payers and providers focused on effective management and improving healthcare costs.

    View details for DOI 10.1111/j.1399-5448.2010.00680.x

    View details for Web of Science ID 000289892200007

    View details for PubMedID 20807368

  • Expression and relevance of TRPS-1: a new GATA transcription factor in breast cancer. Hormones & cancer Chen, J. Q., Bao, Y., Litton, J., Xiao, L., Zhang, H., Warneke, C. L., Wu, Y., Shen, X., Wu, S., Katz, R. L., Sahin, A., Bondy, M., Murray, J. L., Radvanyi, L. 2011; 2 (2): 132–43

    Abstract

    GATA transcription factor family members have been found to play a critical role in the differentiation of many tissue types. For example, GATA-3 has been found to be highly correlated with estrogen receptor alpha (ER) expression and is emerging as one of the "master regulators" in breast ductal epithelial cell differentiation. Recently, we discovered another GATA family member highly prevalent in breast cancer called the trichorhinophalangeal syndrome-1 gene (TRPS-1). Using a quantitative immunohistochemistry (qIHC) approach, we found that TRPS-1 was significantly correlated with ER, PR, GATA-3, as well as HER2 expression. However, TRPS-1 was also found to be expressed in a high proportion of ER(-) ductal epithelial breast cancers (BCs), indicating that it may act as a ductal epithelial cell-specific transcription factor regulating cell fate at some point in the epithelial cell differentiation pathway. In keeping with this hypothesis, we found that TRPS-1 protein expression in BC above a certain threshold using qIHC correlated with markedly improved overall survival. Cox proportional hazards analysis found that both TRPS-1 and ER expression above critical threshold equally predicted for improved survival. Thus, TRPS-1 may be a powerful new positive prognostic marker in BC, and further IHC studies, as well as examination of its molecular function in ductal epithelial cell differentiation in the breast, are warranted. In this regard, data on the role of TRPS-1 in the differentiation of cells from mesenchymal precursors in other tissues, such as kidney metanephric mesenchymal cells, columnar chondrocytes, and osteoblasts, in mouse models may be useful. Indeed, these studies have found that TRPS-1 is a critical regulator of mesenchymal-to-epithelial cell transition. In the mammary gland, the restricted expression of TRPS-1 in human, mouse, and rat ductal epithelial cells suggests that it may also play a similar role during ductal luminal progenitor/stem cell differentiation. We present a model of TRPS-1 action in which it may act upstream of GATA-3 and ER on an earlier ductal epithelial progenitor cell or mammary stem cell during mammary gland development and also helps prevent reversion of ER(+) BC cells back into mesenchymal-like cells. This model predicts that BCs with low or no TRPS-1 expression may inherently be much less differentiated and more aggressive tumors with less favorable prognosis.

    View details for DOI 10.1007/s12672-011-0067-5

    View details for PubMedID 21761336

  • Allergy and glioma risk: test of association by genotype INTERNATIONAL JOURNAL OF CANCER Dobbins, S. E., Hosking, F. J., Shete, S., Armstrong, G., Swerdlow, A., Liu, Y., Yu, R., Lau, C., Schoemaker, M. J., Hepworth, S. J., Muir, K., Bondy, M., Houlston, R. S. 2011; 128 (7): 1736–40

    Abstract

    Although epidemiological studies have suggested an association between atopy and glioma risk, these observations have been based on self-reporting of allergic conditions raising the possibility that associations may be noncausal and arise as a consequence of bias, reverse causation or other artifacts. Genetic information provides an alternative approach to investigate the relationship avoiding such biases. We analyzed 1,878 glioma cases and 3,670 controls for variants at 2q12, 5q12.1, 11q13 and 17q21 that are associated with asthma or eczema risk at p < 5.0 × 10(-7) . The SNP rs7216389, which tags the 3' flanking region of ORMDL3 at 17q21 and has been associated with childhood asthma, was correlated with increased glioma risk (OR = 1.10; 95% CI: 1.01-1.19). These data provide evidence for a correlation between asthma susceptibility and glioma risk and illustrate the value of using genetics as an investigative tool for developing etiological hypotheses.

    View details for DOI 10.1002/ijc.25483

    View details for Web of Science ID 000287159400025

    View details for PubMedID 20503266

    View details for PubMedCentralID PMC6400280

  • Risk factors for oligodendroglial tumors: A pooled international study NEURO-ONCOLOGY McCarthy, B. J., Rankin, K. M., Aldape, K., Bondy, M. L., Brannstrom, T., Broholm, H., Feychting, M., Il'yasova, D., Inskip, P. D., Johansen, C., Mellin, B. S., Ruder, A. M., Butler, M., Scheurer, M. E., Schuz, J., Schwartzbaum, J. A., Wrensch, M. R., Davis, F. G. 2011; 13 (2): 242–50

    Abstract

    Oligodendroglial tumors are rare subtypes of brain tumors and are often combined with other glial tumors in epidemiological analyses. However, different demographic associations and clinical characteristics suggest potentially different risk factors. The purpose of this study was to investigate possible risk factors for oligodendroglial tumors (including oligodendroglioma, anaplastic oligodendroglioma, and mixed glioma). Data from 7 case-control studies (5 US and 2 Scandinavian) were pooled. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age group, gender, and study site. Data on 617 cases and 1260 controls were available for analyses. Using data from all 7 studies, history of allergies and/or asthma was associated with a decreased risk of anaplastic oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9), and history of asthma only was associated with a decreased risk of oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) and anaplastic oligodendroglioma (OR = 0.3; 95% CI: 0.1-0.9). A family history of brain tumors was associated with an increased risk of anaplastic oligodendroglioma (OR = 2.2; 95% CI: 1.1-4.5). Having had chicken pox was associated with a decreased risk of oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9) and anaplastic oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) in the US studies. Although there is some overlap in risk factors between oligodendroglial tumors and gliomas as a group, it is likely that additional factors specific to oligodendroglial tumors have yet to be identified. Large, multi-institution international studies will be necessary to better characterize these etiological risk factors.

    View details for DOI 10.1093/neuonc/noq173

    View details for Web of Science ID 000287002700010

    View details for PubMedID 21149253

    View details for PubMedCentralID PMC3064625

  • Policy Implications of Early Onset Breast Cancer Among Mexican-Origin Women CANCER Miranda, P. Y., Wilkinson, A. V., Etzel, C. J., Zhou, R., Jones, L. A., Thompson, P., Bondy, M. L. 2011; 117 (2): 390–97

    Abstract

    Overall, Latinas are more likely to be diagnosed with a more advanced stage of breast cancer and are 20% more likely to die of breast cancer than non-Hispanic white women. It is estimated that from 2003 to 2006, $82.0 billion in direct medical care expenditures, in addition to 100,000 lives annually, could be saved by eliminating health disparities experienced by Latinos and increasing the use of up to 5 preventive services in the United States. An additional 3700 lives could be saved if 90% of women aged ≥40 years were recently screened for breast cancer.The authors examined the risk for breast cancer in a case-control, population-based sample of Mexican-origin women in Harris County, Texas (n=714), where the rates of breast cancer mortality for Latina women have doubled since 1990.Half of breast cancer cases (n=119) were diagnosed in women aged <50 years. In a multivariate model, women who had a family history of breast cancer (odds ratio [OR], 4.3), who were born in Mexico and had high levels of language acculturation (OR, 2.5), and who did not have health insurance (OR, 1.6) had the highest risk for breast cancer.Because the current results indicated that Mexican-origin women are at high-risk for early onset, premenopausal breast cancer, the authors recommended policies that target screening, education, and treatment to prevent increased disparities in mortality. The authors concluded that the inclusion of community members and policymakers as partners in these endeavors would further safeguard against an increase in cancer health disparities and aid in formulating a policy agenda congruent with scientifically based, community-driven policy efforts that address breast cancer screening, education, and treatment in this vulnerable population.

    View details for DOI 10.1002/cncr.25397

    View details for Web of Science ID 000285976100019

    View details for PubMedID 21319396

    View details for PubMedCentralID PMC3071526

  • False-negative-rate based approach selecting top single-nucleotide polymorphisms in the first stage of a two-stage genome-wide association study STATISTICS AND ITS INTERFACE Huang, Z., Wang, J., Wu, C., Houlston, R. S., Bondy, M. L., Shete, S. 2011; 4 (3): 359–71

    Abstract

    Genome-wide association (GWA) studies, where hundreds of thousands of single-nucleotide polymorphisms (SNPs) are tested simultaneously, are becoming popular for identifying disease loci for common diseases. Most commonly, a GWA study involves two stages: the first stage includes testing the association between all SNPs and the disease and the second stage includes replication of SNPs selected from the first stage to validate associations in an independent sample. The first stage is considered to be more fundamental since the second stage is contingent on the results of the first stage. Selection of SNPs from stage one for genotyping in stage two is typically based on an arbitrary threshold or controlling type I errors. These strategies can be inefficient and have potential to exclude genotyping of disease-associated SNPs in stage two. We propose an approach for selecting top SNPs that uses a strategy based on the false-negative rate (FNR). Using the FNR approach, we proposed the number of SNPs that should be selected based on the observed p-values and a pre-specified multi-testing power in the first stage. We applied our method to simulated data and a GWA study of glioma (a rare form of brain tumor) data. Results from simulation and the glioma GWA indicate that the proposed approach provides an FNR-based way to select SNPs using pre-specified power.

    View details for Web of Science ID 000298000300010

    View details for PubMedID 23060946

    View details for PubMedCentralID PMC3467022

  • Modulation of Glioma Risk and Progression by Dietary Nutrients and Antiinflammatory Agents NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL Kyritsis, A. P., Bondy, M. L., Levin, V. A. 2011; 63 (2): 174–84

    Abstract

    Gliomas are tumors of glial origin formed in the central nervous system and exhibit profound morphological and genetic heterogeneity. The etiology of this heterogeneity involves an interaction between genetic alterations and environmental risk factors. Scientific evidence suggests that certain natural dietary components, such as phytoestrogens, flavonoids, polyunsaturated fatty acids, and vitamins, may exert a protective effect against gliomas by changing the nature of the interaction between genetics and environment. Similarly, certain antiinflammatory drugs and dietary modifications, such as methionine restriction and the adoption of low-calorie or ketogenic diets, may take advantage of glioma and normal glial cells' differential requirements for glucose, methionine, and ketone bodies and may, therefore, be effective as part of preventive or treatment strategies for gliomas. Treatment trials of glioma patients and chemoprevention trials of individuals with a known genetic predisposition to glioma using the most promising of these agents, such as the antiinflammatory drugs curcumin and gamma-linolenic acid, are needed to validate or refute these agents' putative role in gliomas.

    View details for DOI 10.1080/01635581.2011.523807

    View details for Web of Science ID 000287489900002

    View details for PubMedID 21302177

    View details for PubMedCentralID PMC3047463

  • Familial Factors and Inherited Susceptibility to Glioma PRINCIPLES AND PRACTICE OF NEURO-ONCOLOGY: A MULTIDISCIPLINARY APPROACH Melin, B., Bondy, M. L., Mehta, M. P., Chang, S. M., Guha, A., Newton, H. B., Vogelbaum, M. A. 2011: 14–17
  • VARIANTS IN INFLAMMATION PATHWAY GENES ARE ASSOCIATED WITH NEUROCOGNITIVE FUNCTION IN BRAIN TUMOR PATIENTS Scheurer, M. E., Etzel, C. J., Wefel, J. S., Liu, Y., Liang, F., El-Zein, R., Meyers, C. A., Bondy, M. L. OXFORD UNIV PRESS INC. 2010: 27
  • What Can We Learn about Disease Etiology from Case-Case Analyses? Lessons from Breast Cancer CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Martinez, M., Cruz, G. I., Brewster, A. M., Bondy, M. L., Thompson, P. A. 2010; 19 (11): 2710–14

    View details for DOI 10.1158/1055-9965.EPI-10-0742

    View details for Web of Science ID 000283991600002

    View details for PubMedID 20870734

    View details for PubMedCentralID PMC5548092

  • Inflammatory Breast Cancer The Disease, the Biology, the Treatment CA-A CANCER JOURNAL FOR CLINICIANS Robertson, F. M., Bondy, M., Yang, W., Yamauchi, H., Wiggins, S., Kamrudin, S., Krishnamurthy, S., Le-Petross, H., Bidaut, L., Player, A. N., Barsky, S. H., Woodward, W. A., Buchholz, T., Lucci, A., Ueno, N., Cristofanilli, M. 2010; 60 (6): 351–75

    Abstract

    Inflammatory breast cancer (IBC) is a rare and aggressive form of invasive breast cancer accounting for 2.5% of all breast cancer cases. It is characterized by rapid progression, local and distant metastases, younger age of onset, and lower overall survival compared with other breast cancers. Historically, IBC is a lethal disease with less than a 5% survival rate beyond 5 years when treated with surgery or radiation therapy. Because of its rarity, IBC is often misdiagnosed as mastitis or generalized dermatitis. This review examines IBC's unique clinical presentation, pathology, epidemiology, imaging, and biology and details current multidisciplinary management of the disease, which comprises systemic therapy, surgery, and radiation therapy.

    View details for DOI 10.3322/caac.20082

    View details for Web of Science ID 000284242900004

    View details for PubMedID 20959401

  • FACTORS INFLUENCING ADHERENCE TO FOLLOW-UP CARE IN CHILDHOOD CANCER SURVIVORS Ater, J., Cruz, S., Xu, A. H., Okcu, M., Bondy, M. WILEY-LISS. 2010: 942
  • Gamma-radiation sensitivity and polymorphisms in RAD51L1 modulate glioma risk CARCINOGENESIS Liu, Y., Shete, S., Wang, L., El-Zein, R., Etzel, C. J., Liang, F., Armstrong, G., Tsavachidis, S., Gilbert, M. R., Aldape, K. D., Xing, J., Wu, X., Wei, Q., Bondy, M. L. 2010; 31 (10): 1762–69

    Abstract

    DNA strand breaks pose the greatest threat to genomic stability. Genetically determined mutagen sensitivity predisposes individuals to a variety of cancers, including glioma. However, polymorphisms in DNA strand break repair genes that may determine mutagen sensitivity are not well studied in cancer risk, especially in gliomas.We correlated genotype data for tag single-nucleotide polymorphisms (tSNPs) of DNA strand break repair genes with a gamma-radiation-induced mutagen sensitivity phenotype [expressed as mean breaks per cell (B/C)] in samples from 426 glioma patients. We also conducted analysis to assess joint and haplotype effects of single-nucleotide polymorphisms (SNPs) on mutagen sensitivity. We further validate our results in an independent external control group totaling 662 subjects.Of the 392 tSNPs examined, we found that mutagen sensitivity was modified by one tSNP in the EME2 gene and six tSNPs in the RAD51L1 gene (P < 0.01). Among the six RAD51L1 SNPs tested in the validation set, one (RAD51L1 rs2180611) was significantly associated with mutagen sensitivity (P = 0.025). Moreover, we found a significant dose-response relationship between the mutagen sensitivity and the number of adverse tSNP genotypes. Furthermore, haplotype analysis revealed that RAD51L1 haplotypes F-A (zero adverse allele) and F-E (six adverse alleles) exhibited the lowest (0.42) and highest (0.93) mean B/C values, respectively. A similar dose-response relationship also existed between the mutagen sensitivity and the number of adverse haplotypes.These results suggest that polymorphisms in and haplotypes of the RAD51L1 gene, which is involved in the double-strand break repair pathway, modulate gamma-radiation-induced mutagen sensitivity.

    View details for DOI 10.1093/carcin/bgq141

    View details for Web of Science ID 000282750100009

    View details for PubMedID 20610542

    View details for PubMedCentralID PMC2981459

  • Inherited variation in immune genes and pathways and glioblastoma risk CARCINOGENESIS Schwartzbaum, J. A., Xiao, Y., Liu, Y., Tsavachidis, S., Berger, M. S., Bondy, M. L., Chang, J. S., Chang, S. M., Decker, P. A., Ding, B., Hepworth, S. J., Houlston, R. S., Hosking, F. J., Jenkins, R. B., Kosel, M. L., Mccoy, L. S., McKinney, P. A., Muir, K., Patoka, J. S., Prados, M., Rice, T., Robertson, L. B., Schoemaker, M. J., Shete, S., Swerdlow, A. J., Wiemels, J. L., Wiencke, J. K., Yang, P., Wrensch, M. R. 2010; 31 (10): 1770-1777

    Abstract

    To determine whether inherited variations in immune function single-nucleotide polymorphisms (SNPs), genes or pathways affect glioblastoma risk, we analyzed data from recent genome-wide association studies in conjunction with predefined immune function genes and pathways. Gene and pathway analyses were conducted on two independent data sets using 6629 SNPs in 911 genes on 17 immune pathways from 525 glioblastoma cases and 602 controls from the University of California, San Francisco (UCSF) and a subset of 6029 SNPs in 893 genes from 531 cases and 1782 controls from MD Anderson (MDA). To further assess consistency of SNP-level associations, we also compared data from the UK (266 cases and 2482 controls) and the Mayo Clinic (114 cases and 111 controls). Although three correlated epidermal growth factor receptor (EGFR) SNPs were consistently associated with glioblastoma in all four data sets (Mantel-Haenzel P values = 1 × 10⁻⁵ to 4 × 10⁻³), independent replication is required as genome-wide significance was not attained. In gene-level analyses, eight immune function genes were significantly (minP < 0.05) associated with glioblastoma; the IL-2RA (CD25) cytokine gene had the smallest minP values in both UCSF (minP = 0.01) and MDA (minP = 0.001) data sets. The IL-2RA receptor is found on the surface of regulatory T cells potentially contributing to immunosuppression characteristic of the glioblastoma microenvironment. In pathway correlation analyses, cytokine signaling and adhesion-extravasation-migration pathways showed similar associations with glioblastoma risk in both MDA and UCSF data sets. Our findings represent the first systematic description of immune genes and pathways that characterize glioblastoma risk.

    View details for DOI 10.1093/carcin/bgq152

    View details for Web of Science ID 000282750100010

    View details for PubMedID 20668009

    View details for PubMedCentralID PMC2950934

  • A COMPREHENSIVE STUDY OF THE ASSOCIATION BETWEEN THE EGFR AND ERBB2 GENES AND GLIOMA RISK Andersson, U., Scwartzbaum, J., Wiklund, F., Sjostrom, S., Liu, Y., Tsavachidis, S., Ahlbom, A., Auvinen, A., Collatz-Laier, H., Feychting, M., Johansen, C., Kiuru, A., Lonn, S., Schoemaker, M. J., Swerdlow, A. J., Henriksson, R., Bondy, M., Melin, B. OXFORD UNIV PRESS INC. 2010: 17
  • Survey of familial glioma and role of germline p16 (INK4A)/p14 (ARF) and p53 mutation FAMILIAL CANCER Robertson, L. B., Armstrong, G. N., Olver, B. D., Lloyd, A. L., Shete, S., Lau, C., Claus, E. B., Barnholtz-Sloan, J., Lai, R., Il'yasova, D., Schildkraut, J., Bernstein, J. L., Olson, S. H., Jenkins, R. B., Yang, P., Rynerason, A. L., Wrensch, M., McCoy, L., Wienkce, J. K., McCarthy, B., Davis, F., Vick, N. A., Johansen, C., Bodtcher, H., Sadetzki, S., Bruchim, R., Yechezkel, G., Andersson, U., Melin, B. S., Bondy, M. L., Houlston, R. S. 2010; 9 (3): 413–21

    Abstract

    There is increasing recognition of familial propensity to glioma as a distinct clinical entity beyond a few rare syndromes; however its genetic basis is poorly understood. The role of p16(INK4A)/p14(ARF) and p53 mutations in sporadic glioma provides a strong rationale for investigating germline mutations in these genes as a cause of familial glioma. To survey the familial glioma phenotype and examine the contribution of germline mutation in p16(INK4A)/p14(ARF) and p53 to the disease we have analyzed a series of 101 index familial cases collected through the GLIOGENE Consortium (http://braintumor.epigenetic.org/). There was little evidence for within family correlations for tumour histology, suggesting generic susceptibility to glial tumors. We did not detect any functional mutations in p16(INK4A) or p14(ARF). One index case with glioblastoma multiforme (GBM) diagnosed at age 54 and had a family history comprised of a paternal aunt with GBM at age 55, carried the p53 R158H mutation, which is predicted to be functional and has previously been implicated as a cause of Li-Fraumeni syndrome. Our findings provide no evidence that p16(INK4A)/p14(ARF) and p53 mutations contribute significantly to familial glioma.

    View details for DOI 10.1007/s10689-010-9346-5

    View details for Web of Science ID 000280922100024

    View details for PubMedID 20455025

    View details for PubMedCentralID PMC2922430

  • Pathologic Complete Response in Breast Cancer Patients Receiving Anthracycline- and Taxane-Based Neoadjuvant Chemotherapy Evaluating the Effect of Race/Ethnicity CANCER Chavez-MacGregor, M., Litton, J., Chen, H., Giordano, S. H., Hudis, C. A., Wolff, A. C., Valero, V., Hortobagyi, G. N., Bondy, M. L., Gonzalez-Angulo, A. 2010; 116 (17): 4168–77

    Abstract

    The current study was conducted to evaluate the influence of race/ethnicity and tumor subtype in pathologic complete response (pCR) following treatment with neoadjuvant chemotherapy.A total of 2074 patients diagnosed with breast cancer between 1994 and 2008 who were treated with neoadjuvant anthracycline- and taxane-based chemotherapy were included. pCR was defined as no residual invasive cancer in the breast and axilla. The Kaplan-Meier product-limit was used to calculate survival outcomes. Cox proportional hazards models were fitted to determine the relationship of patient and tumor variables with outcome.The median patient age was 50 years; 14.6% of patients were black, were 15.2% Hispanic, 64.3% were white, and 5.9% were of other race. There were no differences in pCR rates among race/ethnicity (12.3% in black, 14.2% in Hispanics, 12.3% in whites, and 11.5% in others, P = .788). Lack of pCR, breast cancer subtype, grade 3 tumors, and lymphovascular invasion were associated with worse recurrence-free survival (RFS) and overall survival (OS) (P

    View details for DOI 10.1002/cncr.25296

    View details for Web of Science ID 000281026000026

    View details for PubMedID 20564153

    View details for PubMedCentralID PMC2954673

  • Genetic variations in EGF and EGFR and glioblastoma outcome NEURO-ONCOLOGY Sjostrom, S., Andersson, U., Liu, Y., Brannstrom, T., Broholm, H., Johansen, C., Collatz-Laier, H., Henriksson, R., Bondy, M., Melin, B. 2010; 12 (8): 815–21

    Abstract

    Few prognostic factors have been associated with glioblastoma survival. We analyzed a complete tagging of the epidermal growth factor (EGF) and EGF receptor (EGFR) gene polymorphisms as potential prognostic factors. Thirty tagging single-nucleotide polymorphisms (SNPs) in EGF and 89 tagging SNPs in EGFR were analyzed for association with survival in 176 glioblastoma cases. Validation analyses were performed for 4 SNPs in a set of 638 glioblastoma patients recruited at The University of Texas M. D. Anderson Cancer Center (MDACC). Three hundred and seventy-four glioblastoma patients aged 50 years or older at diagnosis were subanalyzed to enrich for de novo arising glioblastoma. We found 7 SNPs in haplotype 4 in EGF that were associated with prognosis in glioblastoma patients. In EGFR, 4 of 89 SNPs were significantly associated with prognosis but judged as false positives. Four of the significantly associated EGF polymorphisms in haplotype block 4 were validated in a set from MDACC; however, none of the associations were clearly replicated. rs379644 had a hazard ratio (HR) of 1.19 (0.94-1.51) in the whole population with 18.6 months survival in the risk genotype compared with 24.5 in the reference category. As the median age differed slightly between the 2 study sets, the MDACC cases aged 50 or older at diagnosis were analyzed separately (rs379644, HR 1.32 [0.99-1.78]), which is marginally significant and partially validates our findings. This study is, to our knowledge, the first to perform a comprehensive tagging of the EGF and EGFR genes, and the data give some support that EGF polymorphisms might be associated with poor prognosis. Further confirmation in independent data sets of prospective studies is necessary to establish EGF as prognostic risk factor.

    View details for DOI 10.1093/neuonc/noq018

    View details for Web of Science ID 000280705800007

    View details for PubMedID 20197289

    View details for PubMedCentralID PMC2940681

  • A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk ACTA ONCOLOGICA Andersson, U., Schwartzbaum, J., Wiklund, F., Sjostrom, S., Liu, Y., Tsavachidis, S., Ahlbom, A., Auvinen, A., Collatz-Laier, H., Feychting, M., Johansen, C., Kiuru, A., Lonn, S., Schoemaker, M. J., Swerdlow, A. J., Henriksson, R., Bondy, M., Melin, B. 2010; 49 (6): 767–75

    Abstract

    Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression. We investigated the genetic variants of EGFR, ERBB2, VEGFR and their ligands, EGF and VEGF on glioma and glioblastoma risk. In addition, we evaluated the association of genetic variants of a newly discovered family of genes known to interact with EGFR: LRIG2 and LRIG3 with glioma and glioblastoma risk. Methods. We analyzed 191 tag single nucleotide polymorphisms (SNPs) capturing all common genetic variation of EGF, EGFR, ERBB2, LRIG2, LRIG3, VEGF and VEGFR2 genes. Material from four case-control studies with 725 glioma patients (329 of who were glioblastoma patients) and their 1 610 controls was used. Haplotype analyses were conducted using SAS/Genetics software. Results. Fourteen of the SNPs were significantly associated with glioma risk at p< 0.05, and 17 of the SNPs were significantly associated with glioblastoma risk at p< 0.05. In addition, we found that one EGFR haplotype was related to increased glioblastoma risk at p=0.009, Odds Ratio [OR] = 1.67 (95% confidence interval (CI): 1.14, 2.45). The Bonferroni correction made all p-values non-significant. One SNP, rs4947986 next to the intron/exon boundary of exon 7 in EGFR, was validated in an independent data set of 713 glioblastoma and 2 236 controls, [OR] = 1.42 (95% CI: 1.06,1.91). Discussion. Previous studies show that regulation of the EGFR pathway plays a role in glioma progression but the present study is the first to find that certain genotypes of the EGFR gene may be related to glioblastoma risk. Further studies are required to reinvestigate these findings and evaluate the functional significance.

    View details for DOI 10.3109/0284186X.2010.480980

    View details for Web of Science ID 000280591800003

    View details for PubMedID 20446891

  • Role of Type 1 IFNs in Antiglioma Immunosurveillance-Using Mouse Studies to Guide Examination of Novel Prognostic Markers in Humans CLINICAL CANCER RESEARCH Fujita, M., Scheurer, M. E., Decker, S. A., McDonald, H. A., Kohanbash, G., Kastenhuber, E. R., Kato, H., Bondy, M. L., Ohlfest, J. R., Okada, H. 2010; 16 (13): 3409–19

    Abstract

    We hypothesized that the type 1 IFNs would play a pivotal role in antiglioma immunosurveillance through promotion of type 1 adaptive immunity and suppression of immunoregulatory cells.We induced de novo gliomas in Ifnar1(-/-) (deficient for type 1 IFN receptors) or wild-type mice by intracerebroventricuar transfection of NRas and a short hairpin RNA against P53 using the Sleeping Beauty transposon system. We analyzed the survival of 587 glioma patients for single nucleotide polymorphisms (SNP) in type 1 IFN-related genes.Ifnar1(-/-) mice exhibited accelerated tumor growth and death. Analyses of brain tumor-infiltrating lymphocytes in Ifnar1(-/-) mice revealed an increase of cells positive for CD11b(+)Ly6G(+) and CD4(+)FoxP3(+), which represent myeloid-derived suppressor cells and regulatory T cells, respectively, but a decrease of CD8(+) cytotoxic T lymphocytes (CTLs) compared with wild-type mice. Ifnar1(-/-) mouse-derived glioma tissues exhibited a decrease in mRNA for the CTL-attracting chemokine Cxcl10, but an increase of Ccl2 and Ccl22, both of which are known to attract immunoregulatory cell populations. Dendritic cells generated from the bone marrow of Ifnar1(-/-) mice failed to function as effective antigen-presenting cells. Moreover, depletion of Ly6G(+) cells prolonged the survival of mice with developing gliomas. Human epidemiologic studies revealed that SNPs in IFNAR1 and IFNA8 are associated with significantly altered overall survival of patients with WHO grade 2 to 3 gliomas.The novel Sleeping Beauty-induced murine glioma model led us to discover a pivotal role for the type 1 IFN pathway in antiglioma immunosurveillance and relevant human SNPs that may represent novel prognostic markers.

    View details for DOI 10.1158/1078-0432.CCR-10-0644

    View details for Web of Science ID 000279399200013

    View details for PubMedID 20472682

    View details for PubMedCentralID PMC2896455

  • The functional promoter polymorphism (-842G > C) in the PIN1 gene is associated with decreased risk of breast cancer in non-Hispanic white women 55 years and younger BREAST CANCER RESEARCH AND TREATMENT Han, C. H., Lu, J., Wei, Q., Bondy, M. L., Brewster, A. M., Yu, T., Buchholz, T. A., Arun, B. K., Wang, L. 2010; 122 (1): 243–49

    Abstract

    PIN1, an isomerase that causes conformational changes in proteins, plays an important role in mammary epithelial cell growth both physiologically and pathologically. Thus, genetic variants in the PIN1 gene may alter protein function and cancer risk. We have previously demonstrated an association between a PIN1 promoter variant (-842G>C; rs2233678) and risk of squamous cell carcinoma of the head and neck, a finding supported by additional functional data. In the present study, we genotyped two promoter single nucleotide polymorphisms (SNPs) (-842G>C, rs2233678 and -667T>C, rs2233679) and one synonymous SNP (Gln33Gln; G>A, rs2233682) in exon 2 to evaluate their associations with risk of sporadic breast cancer in non-Hispanic white women 55 years and younger. We found that the carriers of -842C variant alleles had decreased risk of breast cancer with an adjusted odd ratio (OR) of 0.67 and 95% confidence interval (CI) of 0.50-0.90. This reduced risk was more evident in women after reproductive age of 45 (OR = 0.63, 95% CI = 0.42-0.93), ever-smokers (OR = 0.56, 95% CI = 0.36-0.88), and ever-drinkers (OR = 0.67, 95% CI = 0.45-0.99). No such associations were observed for PIN1 -667T>C and PIN1 Gln33Gln. However, the haplotypes of these three SNPs were also associated with reduced risk of breast cancer. In conclusion, the PIN1 polymorphisms may contribute to the etiology of sporadic breast cancer in non-Hispanic white women 55 years and younger. Further validation in large population-based studies is needed.

    View details for DOI 10.1007/s10549-009-0682-9

    View details for Web of Science ID 000278615800029

    View details for PubMedID 20033770

    View details for PubMedCentralID PMC2883663

  • Genetic advances in glioma: susceptibility genes and networks CURRENT OPINION IN GENETICS & DEVELOPMENT Liu, Y., Shete, S., Hosking, F., Robertson, L., Houlston, R., Bondy, M. 2010; 20 (3): 239–44

    Abstract

    Recent advances in human genome studies have opened new avenues for the identification of susceptibility genes for many complex genetic disorders, especially in the field of rare cancers such as glioma. To date, eight glioma susceptibility loci have been identified by candidate gene-association studies: PRKDC G6721T, XRCC1 W399R, PARP1 A762V, MGMT F84L, ERCC1 A8092C, ERCC2 Q751K, EGF +61 A/G, and IL13 R110G. Five loci have been identified by genome-wide association studies: TERT rs2736100, CCDC26 rs4295627, CDKN2A-CDKN2B rs4977756, PHLDB1 rs498872, and RTEL1 rs6010620. Using the Ingenuity Pathway Analysis tool, we investigated whether these 13 susceptibility genes are biologically related. Our data provide not only networks for understanding the biological properties of gliomagenesis but also useful pathway maps for future understanding of disease.

    View details for DOI 10.1016/j.gde.2010.02.001

    View details for Web of Science ID 000279446500007

    View details for PubMedID 20211558

    View details for PubMedCentralID PMC2885452

  • The association between birth order, sibship size and glioma development in adulthood INTERNATIONAL JOURNAL OF CANCER Amirian, E., Scheurer, M. E., Bondy, M. L. 2010; 126 (11): 2752–56

    Abstract

    The etiology of brain tumors is still largely unknown. Previous research indicates that infectious agents and immunological characteristics may influence adult glioma risk. The purpose of our study was to evaluate the effects of birth order and sibship size (total number of siblings), as indicators of the timing and frequency of early life infections, on adult glioma risk using a population of 489 cases and 540 cancer-free controls from the Harris County Brain Tumor Study. Odds ratios for birth order and sibship size were calculated separately from multivariable logistic regression models, adjusting for sex, family history of cancer, education, and age. Each one-unit increase in birth order confers a 13% decreased risk of glioma development in adulthood (OR = 0.87, 95% CI = 0.79-0.97). However, sibship size was not significantly associated with adult glioma status (OR = 0.97, 95% CI = 0.91-1.04). Our study indicates that individuals who were more likely to develop common childhood infections at an earlier age (those with a higher birth order) may be more protected against developing glioma in adulthood. More biological and epidemiological research is warranted to clarify the exact mechanisms through which the timing of common childhood infections and the course of early life immune development affect gliomagenesis.

    View details for DOI 10.1002/ijc.24962

    View details for Web of Science ID 000277347900024

    View details for PubMedID 19830691

    View details for PubMedCentralID PMC2847667

  • Epidemiologic risk factors associated with breast cancer subtypes Bambhroliya, A., Bondy, M., Thompson, P., Sahin, A., Murray, J. L., Zhou, R., Sexton, K., Brewster, A. M. AMER SOC CLINICAL ONCOLOGY. 2010
  • Association of gene copy number alterations in formalin-fixed, paraffin-embedded tumors with prognostic molecular and pathologic tumor subtypes in early-stage breast cancer Murray, J. L., Thompson, P., Tuna, M., Brewster, A. M., Do, K., Edgerton, M. E., Sahin, A., Mills, G. B., Tsachavidis, S., Bondy, M. AMER SOC CLINICAL ONCOLOGY. 2010
  • Investigation of ethnic differences in the prevalence of chromosomal number aberrations of luminal and triple-negative breast cancers associated with risk of recurrence. Brewster, A. M., Thompson, P., Do, K., Sahin, A., Zhang, L., Murray, J. L., Tsachavidis, S., Mills, G. B., Bondy, M. AMER SOC CLINICAL ONCOLOGY. 2010
  • Integration of specific copy number imbalances and prediction models of early-stage breast cancer recurrence. Thompson, P., Do, K., Brewster, A. M., Shim, J., Murray, J. L., Tsachavidis, S., Sahin, A., Mills, G. B., Bondy, M. AMER SOC CLINICAL ONCOLOGY. 2010
  • Trajectories of Neighborhood Poverty and Associations With Subclinical Atherosclerosis and Associated Risk Factors AMERICAN JOURNAL OF EPIDEMIOLOGY Murray, E. T., Roux, A., Carnethon, M., Lutsey, P. L., Ni, H., O'Meara, E. S. 2010; 171 (10): 1099–1108

    Abstract

    The authors used data from the Multi-Ethnic Study of Atherosclerosis and latent trajectory class modeling to determine patterns of neighborhood poverty over 20 years (1980-2000 residential history questionnaires were geocoded and linked to US Census data). Using these patterns, the authors examined 1) whether trajectories of neighborhood poverty were associated with differences in the amount of subclinical atherosclerosis (common carotid intimal-media thickness) and 2) associated risk factors (body mass index, hypertension, diabetes, current smoking) at baseline (January 2000-August 2002). The authors found evidence of 5 stable trajectory groups with differing levels of neighborhood poverty ( approximately 6%, 12%, 20%, 30%, and 45%) and 1 group with 29% poverty in 1980 and approximately 11% in 2000. Mostly for women, higher cumulative neighborhood poverty was generally significantly associated with worse cardiovascular outcomes. Trends generally persisted after adjustment for adulthood socioeconomic position and race/ethnicity, although they were no longer statistically significant. Among women who had moved during the 20 years, the long-term measure had stronger associations with outcomes (except smoking) than a single, contemporaneous measure. Results indicate that cumulative 20-year exposure to neighborhood poverty is associated with greater cardiovascular risk for women. In residentially mobile populations, single-point-in-time measures underestimate long-term effects.

    View details for DOI 10.1093/aje/kwq044

    View details for Web of Science ID 000277728400006

    View details for PubMedID 20423931

    View details for PubMedCentralID PMC2877469

  • Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 Genes Involved in the Double-Strand Break Repair Pathway Predict Glioblastoma Survival JOURNAL OF CLINICAL ONCOLOGY Liu, Y., Shete, S., Etzel, C. J., Scheurer, M., Alexiou, G., Armstrong, G., Tsavachidis, S., Liang, F., Gilbert, M., Aldape, K., Armstrong, T., Houlston, R., Hosking, F., Robertson, L., Xiao, Y., Wiencke, J., Wrensch, M., Andersson, U., Melin, B. S., Bondy, M. 2010; 28 (14): 2467–74

    Abstract

    Glioblastoma (GBM) is the most common and aggressive type of glioma and has the poorest survival. However, a small percentage of patients with GBM survive well beyond the established median. Therefore, identifying the genetic variants that influence this small number of unusually long-term survivors may provide important insight into tumor biology and treatment.Among 590 patients with primary GBM, we evaluated associations of survival with the 100 top-ranking glioma susceptibility single nucleotide polymorphisms from our previous genome-wide association study using Cox regression models. We also compared differences in genetic variation between short-term survivors (STS; or= 36 months), and explored classification and regression tree analysis for survival data. We tested results using two independent series totaling 543 GBMs.We identified LIG4 rs7325927 and BTBD2 rs11670188 as predictors of STS in GBM and CCDC26 rs10464870 and rs891835, HMGA2 rs1563834, and RTEL1 rs2297440 as predictors of LTS. Further survival tree analysis revealed that patients >or= 50 years old with LIG4 rs7325927 (V) had the worst survival (median survival time, 1.2 years) and exhibited the highest risk of death (hazard ratio, 17.53; 95% CI, 4.27 to 71.97) compared with younger patients with combined RTEL1 rs2297440 (V) and HMGA2 rs1563834 (V) genotypes (median survival time, 7.8 years).Polymorphisms in the LIG4, BTBD2, HMGA2, and RTEL1 genes, which are involved in the double-strand break repair pathway, are associated with GBM survival.

    View details for DOI 10.1200/JCO.2009.26.6213

    View details for Web of Science ID 000277389600022

    View details for PubMedID 20368557

    View details for PubMedCentralID PMC2881725

  • Glutathione S-Transferase Polymorphisms Are Associated With Survival in Anaplastic Glioma Patients CANCER Kilburn, L., Okcu, M., Wang, T., Cao, Y., Renfro-Spelman, A., Aldape, K. D., Gilbert, M. R., Bondy, M. 2010; 116 (9): 2242–49

    Abstract

    Glutathione S-transferases (GSTs) are polymorphic enzymes that are responsible for glutathione conjugation of alkylators and scavenging of free radicals created by radiation. GST polymorphisms may result in altered or absent enzyme activity and have been associated with survival in patients with cancer. The authors of this report hypothesized that patients with anaplastic glioma (AG) who have GST genotypes that encode for lower activity enzymes will have longer survival than similar patients who have higher activity genotypes. The current study was performed to investigate the role of GST enzyme polymorphisms in predicting the survival of patients with AG.The medical records of 207 patients with AG from a single cancer center were reviewed retrospectively. Polymorphisms for the GST micro1 (GSTM1), GST theta1 (GSTT1), and GST pi1 (GSTP1) enzymes were identified. Overall survival was compared using the Kaplan-Meier method and Cox proportional hazards analyses adjusting for age, sex, histology, and therapy.Among the patients with oligodendroglial tumors (n = 94), patients who had the GSTT1 null genotype had a 2.9 times increased risk of death (95% confidence interval [CI], 1.3-6.3) compared with patients who had the GSTT1 non-null genotype. Adjustment for 1p/19q status did not change the finding. In the patients who had anaplastic astrocytoma (n = 113), the patients with all GSTP1 genotypes except GSTP1 *B/*B had a 3.8 times increased risk of death (95% CI, 0.5-29.6) compared with patients who had the GSTP1 *B/*B genotype.In patients with anaplastic oligodendroglial tumors, the GSTT1 null genotype may be associated with poor survival, possibly because of modifications in therapy secondary to increased toxicity. This hypothesis is under investigation. In patients with anaplastic astrocytoma, the GSTP1 *B/*B genotype may confer a survival advantage.

    View details for DOI 10.1002/cncr.25006

    View details for Web of Science ID 000277111900024

    View details for PubMedID 20187096

    View details for PubMedCentralID PMC2861043

  • Genetic variants in inflammation pathway genes and asthma in glioma susceptibility NEURO-ONCOLOGY Amirian, E., Liu, Y., Scheurer, M. E., El-Zein, R., Gilbert, M. R., Bondy, M. L. 2010; 12 (5): 444–52

    Abstract

    Single nucleotide polymorphisms (SNPs) in inflammation-related genes have previously been shown to alter risks of developing various cancers. However, the effects of such SNPs on glioma risk remain unclear. We used a multistrategic approach to elucidate the relationship between glioma risk, asthma/allergies, and 23 literature-based functional SNPs in 11 inflammation genes. Genotyping was conducted on 373 histologically confirmed adult glioma patients and 365 cancer-free controls from the Harris County Brain Tumor Study. Deviations from the Hardy-Weinberg equilibrium were assessed using the chi(2)-test, and Akaike's information criterion was used to determine the best genetic model for each SNP. Odds ratios (ORs) were calculated both for each SNP individually and for grouped analyses, examining the effects of the numbers of adverse alleles on glioma risk in participants with and without asthma. In the single-locus analysis of the 23 examined SNPs, 1 pro-inflammatory and 2 anti-inflammatory gene SNPs were significantly associated with glioma risk (COX2/PTGS2, rs20417 [OR = 1.41]; IL10, rs1800896 [OR = 1.57]; and IL13, rs20541 [OR = 0.39], respectively). When we examined the joint effects of the risk-conferring alleles of these 3 SNPs, we found a significant trend indicating that the risk increases as the number of adverse alleles increase (P = .005). Stratifying by asthma status, we found that this dose-response-like trend of increasing risk is only present among those without asthma/allergies (P < .0001). Our study indicates that polymorphisms in inflammation genes are associated with glioma susceptibility, especially when a history of asthma/allergies is absent.

    View details for DOI 10.1093/neuonc/nop057

    View details for Web of Science ID 000276943300004

    View details for PubMedID 20406895

    View details for PubMedCentralID PMC2940617

  • Modulation of Radiation-Induced Genetic Damage by HCMV in Peripheral Blood Lymphocytes from a Brain Tumor Case-Control Study. Cancers Rourke, E. A., Lopez, M. S., Monroy, C. M., Scheurer, M. E., Etzel, C. J., Albrecht, T., Bondy, M. L., El-Zein, R. A. 2010; 2 (2): 420–35

    Abstract

    Human cytomegalovirus (HCMV) infection occurs early in life and viral persistence remains through life. An association between HCMV infection and malignant gliomas has been reported, suggesting that HCMV may play a role in glioma pathogenesis and could facilitate an accrual of genotoxic damage in the presence of g-radiation; an established risk factor for gliomas. We tested the hypothesis that HCMV infection modifies the sensitivity of cells to gamma-radiation-induced genetic damage. We used peripheral blood lymphocytes (PBLs) from 110 glioma patients and 100 controls to measure the level of chromosome damage and cell death. We evaluated baseline, HCMV-, gamma-radiation and HCMV + gamma-radiation induced genetic instability with the comprehensive Cytokinesis-Blocked Micronucleus Cytome (CBMN-CYT). HCMV, similar to radiation, induced a significant increase in aberration frequency among cases and controls. PBLs infected with HCMV prior to challenge with gamma-radiation led to a significant increase in aberrations as compared to baseline, gamma-radiation and HCMV alone. With regards to apoptosis, glioma cases showed a lower percentage of induction following in vitro exposure to gamma-radiation and HCMV infection as compared to controls. This strongly suggests that, HCMV infection enhances the sensitivity of PBLs to gamma-radiation-induced genetic damage possibly through an increase in chromosome damage and decrease in apoptosis.

    View details for DOI 10.3390/cancers2020420

    View details for PubMedID 24281077

  • New Insights Into Susceptibility to Glioma ARCHIVES OF NEUROLOGY Liu, Y., Shete, S., Hosking, F. J., Robertson, L. B., Bondy, M. L., Houlston, R. S. 2010; 67 (3): 275–78

    Abstract

    The study of inherited susceptibility to cancer has been one of the most informative areas of research in the past decade. Most of the cancer genetics studies have been focused on the common tumors such as breast and colorectal cancers. As the allelic architecture of these tumors is unraveled, research attention is turning to other rare cancers such as glioma, which are also likely to have a major genetic component as the basis of their development. In this brief review we discuss emerging data on glioma whole genome-association searches to identify risk loci. Two glioma genome-wide association studies have so far been reported. Our group identified 5 risk loci for glioma susceptibility (TERT rs2736100, CCDC26 rs4295627, CDKN2A/CDKN2B rs4977756, RTEL1 rs6010620, and PHLDB1 rs498872). Wrensch and colleagues provided further evidence to 2 risk loci (CDKN2B rs1412829 and RTEL1 rs6010620) for GBM and anaplastic astrocytoma. Although these data provide the strongest evidence to date for the role of common low-risk variants in the etiology of glioma, the single-nucleotide polymorphisms identified alone are unlikely to be candidates for causality. Identifying the causal variant at each specific locus and its biological impact now poses a significant challenge, contingent on a combination of fine mapping and functional analyses. Finally, we hope that a greater understanding of the biological basis of the disease will lead to the development of novel therapeutic interventions.

    View details for Web of Science ID 000275308600002

    View details for PubMedID 20212223

    View details for PubMedCentralID PMC5929984

  • Quantitative immunohistochemical analysis and prognostic significance of TRPS-1, a new GATA transcription factor family member, in breast cancer. Hormones & cancer Chen, J. Q., Litton, J., Xiao, L., Zhang, H., Warneke, C. L., Wu, Y., Shen, X., Wu, S., Sahin, A., Katz, R., Bondy, M., Hortobagyi, G., Berinstein, N. L., Murray, J. L., Radvanyi, L. 2010; 1 (1): 21–33

    Abstract

    The trichorhinophalangeal syndrome 1 (TRPS-1) gene is a novel GATA transcription factor family member. Previously, using a gene expression profiling and immunohistochemistry (IHC) screen, we identified TRPS-1 as a highly prevalent gene in breast cancer (BC), expressed in >90% of estrogen receptor alpha (ERalpha)(+) and ERalpha(-) BC subtypes. TRPS-1 was also shown to be expressed in prostate cancer where it was shown to play a proapoptotic function during androgen withdrawal possibly through regulating antioxidant metabolism. The role of TRPS-1 and its prognostic significance in hormone-dependent and hormone-independent BC however is not known. In this study, we developed a new quantitative IHC (qIHC) method to further study TRPS-1 as a marker and possible prognostic indicator in BC. By using this method, a quantitative parameter for TRPS-1 expression called a quick score (QS) was derived from the measured labeling index and mean optical density after IHC and applied to a set of 152 stage II/III BC patients from 1993 to 2006 who did not receive preoperative chemotherapy. Associations between QS and tumor characteristics were evaluated using the Kruskal-Wallis test. A wide range of TRPS-1 QS was found among the sample set with higher TRPS-1 QS significantly associated with tumor ERalpha (p=0.023 for QS and p=0.028 for Allred score), progesterone receptor (p=0.009), and GATA-3 (p<0.0001). TRPS-1 QS was also positively associated with HER2 status (p=0.026). Further analysis of different ductal structures in ten BC cases revealed that TRPS-1 expression was expressed at low levels in the remaining normal ducts and in areas of usual ductal hyperplasia but showed marked increase in expression in ductal carcinoma in situ and invasive carcinoma lesions in the tissue. An analysis of TRPS-1 expression in association with overall survival in the 152 stage II/III sample set also revealed that TRPS-1 QS (≥4.0) was significantly associated with improved survival (p=0.0165). Patients with TRPS-1 QS <4 had a hazard ratio of 2 (p=0.019) after univariate Cox proportional hazards analysis. In summary, this new qIHC approach was found to reveal critical differences in TRPS-1 expression in primary BC samples and found that it is a promising prognostic marker that should be further evaluated as a possible tumor suppressor gene facilitating improved survival in different subtypes of BC.

    View details for DOI 10.1007/s12672-010-0008-8

    View details for PubMedID 21761348

  • Comparison of Birth Weight Corrected for Gestational Age and Birth Weight Alone in Prediction of Development of Childhood Leukemia and Central Nervous System Tumors PEDIATRIC BLOOD & CANCER Sprehe, M. R., Barahmani, N., Cao, Y., Wang, T., Forman, M. R., Bondy, M., Okcu, M. 2010; 54 (2): 242–49

    Abstract

    High birth weight (HBW) is an established risk factor for childhood acute lymphoblastic leukemia (ALL). The purpose of this study was to evaluate if birth weight (BW) corrected-for-gestational age is a better predictor than BW alone for occurrence of ALL and other malignancies in children.Birth certificate data of 2,254 children with cancer who were younger than 5 years old at diagnosis and registered at Texas Cancer Registry during 1995-2003 were compared to 11,734 age-matched controls. Multivariable logistic regression was used to compare models with BW corrected-for-gestational age and BW alone.Compared to children who were appropriate for gestational age (AGA), children who were large for gestational age (LGA) at birth had a 1.66 times (95% CI 1.32-2.10) higher odds of ALL. Similarly, children with a BW > or =4,000 g had a 1.5 times (95% CI 1.18-1.89) higher odds for ALL, compared to children who weighed >2,500 and <4,000 g at birth. Using model diagnostics, the model containing BW corrected-for-gestational age was a better predictor than the model with BW alone [Akaike's Information Criterion (AIC) 4,646 vs. 4,658, respectively]. Odds ratios (OR) were similar for LGA children who were <4,000 g and LGA children who were > or =4,000 g (OR = 1.5, 95% CI 0.97-2.5 and OR = 1.67, 95% CI 1.29-2.16, respectively). BW was not an independent risk factor for acute myeloid leukemia or brain tumors.BW corrected-for-gestational age is a better predictor than BW alone of risk for ALL. Future studies using BW variable should incorporate gestational age in their analyses.

    View details for DOI 10.1002/pbc.22308

    View details for Web of Science ID 000273206700013

    View details for PubMedID 19813253

    View details for PubMedCentralID PMC2795053

  • Biomarker Expression Can Identify Biologically Distinct Categories of Invasive Breast Cancer Shim, J. Y., Zhou, R., Thompson, P. A., Brewster, A. M., Murray, J. L., Edgerton, M. E., Karadag, N., Bondy, M. L., Sahin, A. NATURE PUBLISHING GROUP. 2010: 72A
  • Biomarker Expression Can Identify Biologically Distinct Categories of Invasive Breast Cancer Shim, J. Y., Zhou, R., Thompson, P. A., Brewster, A. M., Murray, J. L., Edgerton, M. E., Karadag, N., Bondy, M. L., Sahin, A. NATURE PUBLISHING GROUP. 2010: 72A
  • Inherited predisposition to glioma NEURO-ONCOLOGY Kyritsis, A. P., Bondy, M. L., Rao, J. S., Sioka, C. 2010; 12 (1): 104–13

    Abstract

    In gliomas, germline gene alterations play a significant role during malignant transformation of progenitor glial cells, at least for families with occurrence of multiple cancers or with specific hereditary cancer syndromes. Scientific evidence during the last few years has revealed several constitutive genetic abnormalities that may influence glioma formation. These germline abnormalities are manifested as either gene polymorphisms or hemizygous mutations of key regulatory genes that are involved either in DNA repair or in apoptosis. Such changes, among others, include hemizygous alterations of the neurofibromatosis 1 (NF1) and p53 genes that are involved in apoptotic pathways, and alterations in multiple DNA repair genes such as mismatch repair (MMR) genes, x-ray cross-complementary genes (XRCC), and O6-methylguanine-DNA methyltransferase (MGMT) genes. Subsequent cellular changes include somatic mutations in cell cycle regulatory genes and genes involved in angiogenesis and invasion, leading eventually to tumor formation in various stages. Future molecular diagnosis may identify new genomic regions that could harbor genes important for glioma predisposition and aid in the early diagnosis of these patients and genetic counseling of their families.

    View details for DOI 10.1093/neuonc/nop011

    View details for Web of Science ID 000273781300014

    View details for PubMedID 20150373

    View details for PubMedCentralID PMC2940552

  • The evolving discipline of molecular epidemiology of cancer CARCINOGENESIS Spitz, M. R., Bondy, M. L. 2010; 31 (1): 127–34

    Abstract

    Classical epidemiologic studies have made seminal contributions to identifying the etiology of most common cancers. Molecular epidemiology was conceived of as an extension of traditional epidemiology to incorporate biomarkers with questionnaire data to further our understanding of the mechanisms of carcinogenesis. Early molecular epidemiologic studies employed functional assays. These studies were hampered by the need for sequential and/or prediagnostic samples, viable lymphocytes and the uncertainty of how well these functional data (derived from surrogate lymphocytic tissue) reflected events in the target tissue. The completion of the Human Genome Project and Hapmap Project, together with the unparalleled advances in high-throughput genotyping revolutionized the practice of molecular epidemiology. Early studies had been constrained by existing technology to use the hypothesis-driven candidate gene approach, with disappointing results. Pathway analysis addressed some of the concerns, although the study of interacting and overlapping gene networks remained a challenge. Whole-genome scanning approaches were designed as agnostic studies using a dense set of markers to capture much of the common genome variation to study germ-line genetic variation as risk factors for common complex diseases. It should be possible to exploit the wealth of these data for pharmacogenetic studies to realize the promise of personalized therapy. Going forward, the temptation for epidemiologists to be lured by high-tech 'omics' will be immense. Systems Epidemiology, the observational prototype of systems biology, is an extension of classical epidemiology to include powerful new platforms such as the transcriptome, proteome and metabolome. However, there will always be the need for impeccably designed and well-powered epidemiologic studies with rigorous quality control of data, specimen acquisition and statistical analysis.

    View details for DOI 10.1093/carcin/bgp246

    View details for Web of Science ID 000273493100014

    View details for PubMedID 20022891

    View details for PubMedCentralID PMC2802669

  • A Progress Review of the Inflammatory Breast Cancer Registry at the University of Texas MD Anderson Cancer Center Bondy, M., Cristofanilli, M., El-Zein, R., Wiggins, S., Lara, J., Jackson, S. AMER ASSOC CANCER RESEARCH. 2009: 616S
  • Risk analysis of severe myelotoxicity with temozolomide: The effects of clinical and genetic factors NEURO-ONCOLOGY Armstrong, T. S., Cao, Y., Scheurer, M. E., Vera-Bolanos, E., Manning, R., Okcu, M. F., Bondy, M., Zhou, R., Gilbert, M. R. 2009; 11 (6): 825–32

    Abstract

    A benefit of temozolomide (TMZ) is that myelotoxicity is uncommon. Recently, several small series have reported significant myelotoxicity resulting in treatment delays or death. The ability to predict risk of myelotoxicity may influence patient care. We retrospectively reviewed 680 malignant glioma patients and developed a clinical risk formula for myelotoxicity for each gender by logistic regression. The variables that remained were assigned a score of 1 and added together for a final risk score. Women experienced more myelotoxicity than did men (p = 0.015). For males, risk factors included body surface area (BSA) > or = 2 m(2) (odds ratio [OR] = 2.712, p = 0.04), not on steroids (OR = 2.214, p = 0.06), and on bowel medication (OR = 3.955, p = 0.008). For females, final factors included no prior chemotherapy (OR = 3.727, p = 0.001), creatinine > or = 1 mg/dl (OR = 6.08, p = 0.002), platelets < 270,000/mm(3) (OR = 2.438, p = 0.03), BSA < 2 m(2) (OR = 4.178, p = 0.04), not on medication for gastroesophageal reflux disease (OR = 2.942, p = 0.01), and on analgesics (OR = 2.169, p = 0.05). Age was included because of observable trends. Risk of developing myelotoxicity ranged from 0% to 33% (male) and from 0% to 100% (females). Polymorphisms in NQO1 (NAD(P)H dehydrogenase, quinone 1), MGMT (O(6)-methylguanine-DNA methyltransferase), and GSTP1 (glutathione S-transferase pi 1) were related to risk of developing myelotoxicity in a subset of patients. Myelotoxicity with TMZ is a significant clinical issue for those at risk. Use of a clinical model to predict risk and evaluation of identified genetic polymorphisms related to myelotoxicity may allow for individualized dosing, optimizing patient management.

    View details for DOI 10.1215/15228517-2008-120

    View details for Web of Science ID 000272974100012

    View details for PubMedID 19179423

    View details for PubMedCentralID PMC2802402

  • Exposure to Smoking Imagery in the Movies and Experimenting with Cigarettes among Mexican Heritage Youth CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Wilkinson, A. V., Spitz, M. R., Prokhorov, A. V., Bondy, M. L., Shete, S., Sargent, J. D. 2009; 18 (12): 3435–43

    Abstract

    There is growing evidence that an adolescent's decision to try cigarettes is influenced by level of exposure to movies in which smoking is portrayed. Less is known about how ethnicity affects this process. We examined whether acculturation and/or country of birth influence the relationship between exposure to smoking imagery in the movies and experimenting with cigarettes among Mexican origin youth. We prospectively followed 1,328 Mexican origin adolescents ages 11 to 13 years at baseline. We assessed which of 50 movies (randomly selected from a pool of 250 popular contemporary movies released from 1999 to 2004 and content analyzed for smoking) adolescents had seen. Smoking behavior was assessed at baseline and at 6-month intervals over 24 months. Ten percent of the adolescents had experimented at baseline; 17% tried subsequently. Multivariate analyses revealed, as exposure to smoking imagery in the movies increased, the chances of having ever experimented [adjusted odds ratio (AOR) = 1.27; 95% confidence interval (CI), 1.10-1.48] and of being a new experimenter (AOR = 1.19; 95% CI, 1.01-1.40) increased, equivalent to a 4.2% increased risk of ever and a 3.0% increased risk of new experimenting for each additional quartile of movie exposure. This effect was moderated by country of birth. For Mexican-born youth, exposure to smoking imagery in the movies was the strongest independent predictor of new experimentation (AOR = 1.52; 95% CI, 1.14-2.05). For U.S.-born youth, we observed a ceiling effect: the percent of experimenters increased with increasing exposure, and then flattened. Among Mexican-born youth, exposure to smoking imagery in the movies may be an important part of the acculturation process associated with smoking initiation.

    View details for DOI 10.1158/1055-9965.EPI-09-0766

    View details for Web of Science ID 000272519800024

    View details for PubMedID 19959693

    View details for PubMedCentralID PMC2791895

  • Cognitive Susceptibility to Smoking: Two Paths to Experimenting among Mexican Origin Youth CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Spelman, A. R., Spitz, M. R., Kelder, S. H., Prokhorov, A. V., Bondy, M. L., Frankowski, R. F., Wilkinson, A. V. 2009; 18 (12): 3459–67

    Abstract

    Cognitive susceptibility to smoking, defined as the lack of a firm commitment not to smoke in the future or if offered a cigarette by a friend, begins in childhood and is an early phase in the transition from never to ever smoking. Our objectives were to examine susceptibility to smoking and other psychosocial risk factors for experimentation with cigarettes among Mexican origin adolescents and to determine whether susceptibility status moderates the relationship between established risk factors for experimentation with cigarettes and future experimentation. We examined susceptibility and several psychosocial factors associated with susceptibility as baseline predictors of experimentation after 3 years of follow-up among 964 Mexican origin girls and boys between 11 and 13 years of age from the Houston metropolitan area. Participants were recruited between May 2005 and October 2006 and reported that they had never experimented with cigarettes at baseline. Baseline susceptibility and experimentation rates were 23% and 9%, respectively, whereas the follow-up experimentation rate, among those who had not experimented at baseline, was 22%. Susceptible adolescents at baseline were 2.6 times more likely to have experimented with cigarettes by follow-up. Baseline susceptibility moderated the relationship between experimentation at follow-up and the psychosocial risk factors assessed at baseline. Susceptibility is a valid and strong marker for the transition to experimentation for Mexican origin adolescents. Our results suggest that tailoring primary prevention programs by a youth's susceptibility status may increase the efficacy of prevention efforts among Mexican origin youth.

    View details for DOI 10.1158/1055-9965.EPI-09-0765

    View details for Web of Science ID 000272519800027

    View details for PubMedID 19959696

    View details for PubMedCentralID PMC3183967

  • Construction of an N-nitroso database for assessing dietary intake Stuff, J. E., Goh, E. T., Barrera, S. L., Bondy, M. L., Forman, M. R. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2009: S42–S47

    Abstract

    Dietary N-nitroso compounds are carcinogens synthesized during food processing from two main classes of precursors, oxides of nitrogen and amines or amides. Quantification of the dietary intake of N-nitroso compounds is significant to human cancers, including those of the stomach and upper gastro-intestinal tract, colon, and brain. Previous studies investigating these cancers primarily used proxy estimates of N-nitroso intake and not a full and complete database. In this report, we describe the development of a database to be used in conjunction with a food frequency questionnaire (FFQ) or twenty-four hour dietary records. Published analytical data for N-nitroso compounds were compiled and evaluated for inclusion in the database. The final database consisted of 23 different N-nitroso compounds for 500 foods from 39 different food subgroups. Next, database foods were matched to foods in a standard FFQ by imputation, or calculated value, or assumed zero. Using the FFQ modified with N-nitroso values, we evaluated the ability to compute N-nitroso intakes for a sample of healthy control subjects of cancer epidemiological studies. N-nitroso content of food items ranged from <0.01μg/100 g. to 142 μg/100 g and the richest sources were sausage, smoked meats, bacon, and luncheon meats. The database is useful to quantify N-nitroso intake for observational and epidemiological studies.

    View details for DOI 10.1016/j.jfca.2009.01.008

    View details for Web of Science ID 000273379000008

    View details for PubMedID 20161416

    View details for PubMedCentralID PMC2786176

  • Pubertal Development in Mexican American Girls: The Family's Perspective QUALITATIVE HEALTH RESEARCH Jean, R., Bondy, M. L., Wilkinson, A. V., Forman, M. R. 2009; 19 (9): 1210–22

    Abstract

    Mexican American (MA) girls are entering puberty earlier than in the past, yet few studies have explored the perceptions surrounding puberty among this group. We conducted separate focus groups for fathers, mothers, and daughters aged 6 to 12 years to explore perceptions of body image, pubertal development, communications, and sources of puberty-related information in MA participants. Our results revealed parental concerns about daughters' weight and pubertal development, as well as differences in their communication with their daughters. Although both parents willingly discussed pubertal issues concerning their daughters, mothers had a more active role in conveying pubertal information to daughters. Among the girls, there was a gap in knowledge about the pubertal process between the younger and older girls. Our findings present opportunities and challenges for addressing obesity as a pubertal risk factor in MA girls; however, more studies are needed to understand family beliefs and sociocultural dynamics surrounding puberty in MAs.

    View details for DOI 10.1177/1049732309344326

    View details for Web of Science ID 000269752900004

    View details for PubMedID 19690203

    View details for PubMedCentralID PMC3183834

  • Genome-wide association study identifies five susceptibility loci for glioma NATURE GENETICS Shete, S., Hosking, F. J., Robertson, L. B., Dobbins, S. E., Sanson, M., Malmer, B., Simon, M., Marie, Y., Boisselier, B., Delattre, J., Hoang-Xuan, K., El Hallani, S., Idbaih, A., Zelenika, D., Andersson, U., Henriksson, R., Bergenheim, A., Feychting, M., Lonn, S., Ahlbom, A., Schramm, J., Linnebank, M., Hemminki, K., Kumar, R., Hepworth, S. J., Price, A., Armstrong, G., Liu, Y., Gu, X., Yu, R., Lau, C., Schoemaker, M., Muir, K., Swerdlow, A., Lathrop, M., Bondy, M., Houlston, R. S. 2009; 41 (8): 899–U54

    Abstract

    To identify risk variants for glioma, we conducted a meta-analysis of two genome-wide association studies by genotyping 550K tagging SNPs in a total of 1,878 cases and 3,670 controls, with validation in three additional independent series totaling 2,545 cases and 2,953 controls. We identified five risk loci for glioma at 5p15.33 (rs2736100, TERT; P = 1.50 x 10(-17)), 8q24.21 (rs4295627, CCDC26; P = 2.34 x 10(-18)), 9p21.3 (rs4977756, CDKN2A-CDKN2B; P = 7.24 x 10(-15)), 20q13.33 (rs6010620, RTEL1; P = 2.52 x 10(-12)) and 11q23.3 (rs498872, PHLDB1; P = 1.07 x 10(-8)). These data show that common low-penetrance susceptibility alleles contribute to the risk of developing glioma and provide insight into disease causation of this primary brain tumor.

    View details for DOI 10.1038/ng.407

    View details for Web of Science ID 000268432900013

    View details for PubMedID 19578367

    View details for PubMedCentralID PMC4501476

  • N-Nitroso Compounds: Assessing Agreement between Food Frequency Questionnaires and 7-Day Food Records JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION Stuff, J. E., Goh, E. T., Barrera, S. L., Bondy, M. L., Forman, M. R. 2009; 109 (7): 1179–83

    Abstract

    N-nitroso compounds are recognized as important dietary carcinogens. Accurate assessment of N-nitroso intake is fundamental to advancing research regarding its role with cancer. Previous studies have not used a quantitative database to estimate the intake of these compounds in a US population.To address this gap, a database of N-nitroso values was developed in conjunction with an existing food frequency questionnaire (FFQ). In this article we report on the relative validity of the FFQ instrument modified to estimate intake of N-nitroso compounds.Intake estimates of 23 N-nitroso compounds from the FFQ were compared with those from 7-day food records in a cross-sectional study conducted from January 2005 through June 2006.A sample of 98 healthy adult subjects (aged 50.42+/-12.84 years) completed an FFQ and then recorded foods and beverages consumed on 7-day food records.Crude and energy-adjusted N-nitroso compounds intakes were significantly higher in the FFQ than the 7-day food records (P<0.001). Spearman correlations for crude and energy-adjusted N-nitroso intakes ranged from 0.004 to 0.48. By tertiles of N-nitiroso compounds, there was moderate agreement (kappa>0.30) for five compounds. Higher estimates of N-nitroso compounds by FFQ was explained by a greater proportion of subjects who reported eating foods high in N-nitroso compounds on FFQ than reported on 7-day food records.The modified FFQ with N-nitroso values is a useful tool for assessing N-nitroso intakes relative to a group, and captures all food items with N-nitroso compounds, including those foods with high concentrations and eaten sporadically.

    View details for DOI 10.1016/j.jada.2009.04.006

    View details for Web of Science ID 000267847400014

    View details for PubMedID 19559134

    View details for PubMedCentralID PMC2736544

  • Premenopausal Breast Cancer: Estrogen Receptor Status and Insulin-Like Growth Factor-I (IGF-I), Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3), and Leptin BREAST JOURNAL Eng-Wong, J., Perkins, S. N., Bondy, M., Li, D., Singletary, S. E., Nunez, N., Hursting, S., Chang, S. 2009; 15 (4): 426-428
  • Molecular Epidemiology of Primary Brain Tumors NEUROTHERAPEUTICS Gu, J., Liu, Y., Kyritsis, A. P., Bondy, M. L. 2009; 6 (3): 427–35

    Abstract

    Although primary brain tumors (PBTs) are generally considered to be a multifactorial disorder, understanding the genetic basis and etiology of the disease is essential for PBT risk assessment. Understanding of the genetic susceptibility for PBT has come from studies of rare genetic syndromes, linkage analysis, family aggregation, early-onset pediatric cases, and mutagen sensitivity. There are currently no effective markers to assess biological dose of exposures and genetic heterogeneity. The priorities recently recommended by the Brain Tumor Epidemiology Consortium emphasized the need for expanding research in genetics and molecular epidemiology. In this article, we review the literature to identify molecular epidemiologic case-control studies of PBTs that were hypothesis-driven and focused on four hypothesized candidate pathways: DNA repair, cell cycle, metabolism, and inflammation. We summarize the results in terms of genetic associations of single nucleotide polymorphisms of these pathways. We also discuss future research directions based on available evidence and technologies, and conclude that high resolution whole genome approach with significantly large sample size could rapidly advance our understanding of the genetic etiology of PBTs. Literature searches were done on PubMed in March 2009 with the terms glioma, glioblastoma, brain tumor, association, and polymorphism, and we only reviewed English language publications.

    View details for DOI 10.1016/j.nurt.2009.05.001

    View details for Web of Science ID 000267581800002

    View details for PubMedID 19560733

    View details for PubMedCentralID PMC5084179

  • Body Mass Index and Risk, Age of Onset, and Survival in Patients With Pancreatic Cancer JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Li, D., Morris, J. S., Liu, J., Hassan, M. M., Day, R., Bondy, M. L., Abbruzzese, J. L. 2009; 301 (24): 2553–62

    Abstract

    Obesity has been implicated as a risk factor for pancreatic cancer.To demonstrate the association of excess body weight across an age cohort and the risk, age of onset, and overall survival of patients with pancreatic cancer.A case-control study of 841 patients with pancreatic adenocarcinoma and 754 healthy individuals frequency matched by age, race, and sex. The study was conducted at a university cancer center in the United States from 2004 to 2008. Height and body weight histories were collected by personal interview starting at ages 14 to 19 years and over 10-year intervals progressing to the year prior to recruitment in the study.The associations between patients' body mass index (BMI) and risk of pancreatic cancer, age at onset, and overall survival were examined by unconditional logistic regression, linear regression, and Cox proportional hazard regression models, respectively.Individuals who were overweight (a BMI of 25-29.9) from the ages of 14 to 39 years (highest odds ratio [OR], 1.67; 95% confidence interval [CI], 1.20-2.34) or obese (a BMI > or = 30) from the ages of 20 to 49 years (highest OR, 2.58; 95% CI, 1.70-3.90) had an associated increased risk of pancreatic cancer, independent of diabetes status. The association was stronger in men (adjusted OR, 1.80; 95% CI, 1.45-2.23) by mean BMI from the ages of 14 to 59 years than in women (adjusted OR, 1.32; 95% CI, 1.02-1.70) and in ever smokers (adjusted OR, 1.75; 95% CI, 1.37-2.22) than in never smokers (adjusted OR, 1.46; 95% CI, 1.16-1.84). The population-attributable risk percentage of pancreatic cancer based on the mean BMI from the ages of 14 to 59 years was 10.3% for never smokers and 21.3% for ever smokers. Individuals who were overweight or obese from the ages of 20 to 49 years had an earlier onset of pancreatic cancer by 2 to 6 years (median age of onset was 64 years for patients with normal weight, 61 years for overweight patients [P = .02], and 59 years for obese patients [P < .001]). Compared with those with normal body weight and after adjusting for all clinical factors, individuals who were overweight or obese from the ages of 30 to 79 years or in the year prior to recruitment had reduced overall survival of pancreatic cancer regardless of disease stage and tumor resection status (overweight patients: hazard ratio, 1.26 [95% CI, 0.94-1.69], P = .04; obese patients: hazard ratio, 1.86 [95% CI, 1.35-2.56], P < .001).Overweight or obesity during early adulthood was associated with a greater risk of pancreatic cancer and a younger age of disease onset. Obesity at an older age was associated with a lower overall survival in patients with pancreatic cancer.

    View details for DOI 10.1001/jama.2009.886

    View details for Web of Science ID 000267266500020

    View details for PubMedID 19549972

    View details for PubMedCentralID PMC2760963

  • Association of Body Mass Index with Risk, Age of Onset and Survival of Pancreatic Cancer Li, D., Morris, J., Liu, J., Hassan, M., Day, R., Bondy, M., Evans, D., Abbruzzese, J. AMER ASSOC CANCER RESEARCH. 2009
  • Influence of Subjective Social Status on the Relationship Between Positive Outcome Expectations and Experimentation JOURNAL OF ADOLESCENT HEALTH Wilkinson, A. V., Shete, S., Vasudevan, V., Prokhorov, A. V., Bondy, M. L., Spitz, M. R. 2009; 44 (4): 342–48

    Abstract

    In Texas, Mexican American (MA) adolescents, and in particular boys, are at increased risk for experimenting with cigarettes compared with their black or white counterparts. Positive outcome expectations (POE), that is, the functional social significance ascribed to cigarettes, and subjective social status (SSS), that is, the adolescents' subjective views of where they lie in the school-based social hierarchy, are independent predictors of smoking. The goal of this study was to test the hypothesis that SSS moderates the relationship between POE and experimentation with cigarettes.Moderating effects of SSS were examined using a between-subjects, 2 x 2 analysis of variance and unconditional logistic regression analyses. Using a prospective study design, we followed 1142 MA adolescents aged 11-13 years. Participants completed a baseline survey at home, which assessed POE, SSS, and smoking and were followed via telephone at 6-month intervals over a 12-month period to assess changes in smoking behavior.At follow-up, there were 99 new experimenters. Consistent with our hypothesis, adolescents who reported moderate-low SSS and who held POE at baseline were more likely to have experimented with cigarettes at either follow-up evaluation than their peers with moderate-low SSS who held less POE (odds ratio [OR], 1.92, 95% confidence interval [95% CI], 1.02-3.58). There was no association between outcome expectations and experimenting among adolescents with high SSS (OR, 1.79, CI, .73-4.36). Low SSS boys were more likely to experiment than girls and high SSS boys.The results of this study indicate that adolescents with moderate-low SSS hold different outcome expectations about smoking than their higher SSS peers. The results underscore the possibility that moderate-low SSS adolescents view behaviors such as smoking as a way to achieve higher SSS and thereby increase their peer social standing. Our results suggest that, in addition to tailoring intervention efforts by gender, placing adolescents of similar social standing to one another within the school into intervention groups that are led by a peer-nominated peer may increase the overall effectiveness of these peer-led prevention efforts.

    View details for DOI 10.1016/j.jadohealth.2008.08.003

    View details for Web of Science ID 000264778400006

    View details for PubMedID 19306792

    View details for PubMedCentralID PMC2705959

  • Associations between Polymorphisms in DNA Repair Genes and Glioblastoma CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION McKean-Cowdin, R., Barnholtz-Sloan, J., Inskip, P. D., Ruder, A. M., Butler, M., Rajaraman, P., Razavi, P., Patoka, J., Wiencke, J. K., Bondy, M. L., Wrensch, M. 2009; 18 (4): 1118–26

    Abstract

    A pooled analysis was conducted to examine the association between select variants in DNA repair genes and glioblastoma multiforme, the most common and deadliest form of adult brain tumors. Genetic data for approximately 1,000 glioblastoma multiforme cases and 2,000 controls were combined from four centers in the United States that have conducted case-control studies on adult glioblastoma multiforme, including the National Cancer Institute, the National Institute for Occupational Safety and Health, the University of Texas M. D. Anderson Cancer Center, and the University of California at San Francisco. Twelve DNA repair single-nucleotide polymorphisms were selected for investigation in the pilot collaborative project. The C allele of the PARP1 rs1136410 variant was associated with a 20% reduction in risk for glioblastoma multiforme (odds ratio(CT or CC), 0.80; 95% confidence interval, 0.67-0.95). A 44% increase in risk for glioblastoma multiforme was found for individuals homozygous for the G allele of the PRKDC rs7003908 variant (odds ratio(GG), 1.44; 95% confidence interval, 1.13-1.84); there was a statistically significant trend (P = 0.009) with increasing number of G alleles. A significant, protective effect was found when three single-nucleotide polymorphisms (ERCC2 rs13181, ERCC1 rs3212986, and GLTSCR1 rs1035938) located near each other on chromosome 19 were modeled as a haplotype. The most common haplotype (AGC) was associated with a 23% reduction in risk (P = 0.03) compared with all other haplotypes combined. Few studies have reported on the associations between variants in DNA repair genes and brain tumors, and few specifically have examined their impact on glioblastoma multiforme. Our results suggest that common variation in DNA repair genes may be associated with risk for glioblastoma multiforme.

    View details for DOI 10.1158/1055-9965.EPI-08-1078

    View details for Web of Science ID 000265125000013

    View details for PubMedID 19318434

    View details for PubMedCentralID PMC2667563

  • High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays BMC MEDICAL GENOMICS Wang, Y., Carlton, V. H., Karlin-Neumann, G., Sapolsky, R., Zhang, L., Moorhead, M., Wang, Z. C., Richardson, A. L., Warren, R., Walther, A., Bondy, M., Sahin, A., Krahe, R., Tuna, M., Thompson, P. A., Spellman, P. T., Gray, J. W., Mills, G. B., Faham, M. 2009; 2: 8

    Abstract

    A major challenge facing DNA copy number (CN) studies of tumors is that most banked samples with extensive clinical follow-up information are Formalin-Fixed Paraffin Embedded (FFPE). DNA from FFPE samples generally underperforms or suffers high failure rates compared to fresh frozen samples because of DNA degradation and cross-linking during FFPE fixation and processing. As FFPE protocols may vary widely between labs and samples may be stored for decades at room temperature, an ideal FFPE CN technology should work on diverse sample sets. Molecular Inversion Probe (MIP) technology has been applied successfully to obtain high quality CN and genotype data from cell line and frozen tumor DNA. Since the MIP probes require only a small (approximately 40 bp) target binding site, we reasoned they may be well suited to assess degraded FFPE DNA. We assessed CN with a MIP panel of 50,000 markers in 93 FFPE tumor samples from 7 diverse collections. For 38 FFPE samples from three collections we were also able to asses CN in matched fresh frozen tumor tissue.Using an input of 37 ng genomic DNA, we generated high quality CN data with MIP technology in 88% of FFPE samples from seven diverse collections. When matched fresh frozen tissue was available, the performance of FFPE DNA was comparable to that of DNA obtained from matched frozen tumor (genotype concordance averaged 99.9%), with only a modest loss in performance in FFPE.MIP technology can be used to generate high quality CN and genotype data in FFPE as well as fresh frozen samples.

    View details for DOI 10.1186/1755-8794-2-8

    View details for Web of Science ID 000272744600001

    View details for PubMedID 19228381

    View details for PubMedCentralID PMC2649948

  • Method of detection is a prognostic factor for outcome among women diagnosed with early stage breast cancer Brewster, A. M., Thompson, P. A., Cao, Y., Murray, J. L., Stewart, M. M., Berry, D. A., Bondy, M. L. AMER ASSOC CANCER RESEARCH. 2009: 302S
  • Tumor-associated epilepsy and glioma: Are there common genetic pathways? ACTA ONCOLOGICA Berntsson, S., Malmer, B., Bondy, M. L., Qu, M., Smits, A. 2009; 48 (7): 955–63

    Abstract

    Patients with glioma exhibit a great variability in clinical symptoms apart from variations in response to therapy and survival. Many patients present with epileptic seizures at disease onset, especially in case of low-grade gliomas, but not all have seizures. A large proportion of patients develop refractory seizures. It is likely that the variability in epileptic symptoms cannot exclusively be explained by tumor-related factors, but rather reflects complex interaction between tumor-related, environmental and hereditary factors.No data exist on susceptibility genes associated with epileptic symptoms in patients with glioma. However, an increasing number of candidate genes have been proposed for other focal epilepsies such as temporal lobe epilepsy. Some of the susceptibility candidate genes associated with focal epilepsy may contribute to epileptic symptoms also in patients with glioma.This review presents an update on studies on genetic polymorphisms and focal epilepsy and brings forward putative candidate genes for tumor-associated epilepsy, based on the assumption that common etiological pathways may exist for glioma development and glioma-associated seizures. Conclusion. Genes involved in the immune response, in synaptic transmission and in cell cycle control are discussed that may play a role in the pathogenesis of tumor growth as well as epileptic symptoms in patients with gliomas.

    View details for DOI 10.1080/02841860903104145

    View details for Web of Science ID 000271228400002

    View details for PubMedID 19639468

    View details for PubMedCentralID PMC6436628

  • Association and Interactions between DNA Repair Gene Polymorphisms and Adult Glioma CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Liu, Y., Scheurer, M. E., El-Zein, R., Cao, Y., Do, K., Gilbert, M., Aldape, K. D., Wei, Q., Etzel, C., Bondy, M. L. 2009; 18 (1): 204–14

    Abstract

    It is generally accepted that glioma develops through accumulation of genetic alterations. We hypothesized that polymorphisms of candidate genes involved in the DNA repair pathways may contribute to susceptibility to glioma. To address this possibility, we conducted a study on 373 Caucasian glioma cases and 365 cancer-free Caucasian controls to assess associations between glioma risk and 18 functional single-nucleotide polymorphisms in DNA repair genes. We evaluated potential gene-gene and gene-environment interactions using a multianalytic strategy combining logistic regression, multifactor dimensionality reduction and classification and regression tree approaches. In the single-locus analysis, six single-nucleotide polymorphisms [ERCC1 3' untranslated region (UTR), XRCC1 R399Q, APEX1 E148D, PARP1 A762V, MGMT F84L, and LIG1 5'UTR] showed a significant association with glioma risk. In the analysis of cumulative genetic risk of multiple single-nucleotide polymorphisms, a significant gene-dosage effect was found for increased glioma risk with increasing numbers of adverse genotypes involving the aforementioned six single-nucleotide polymorphisms (P(trend) = 0.0004). Furthermore, the multifactor dimensionality reduction and classification and regression tree analyses identified MGMT F84L as the predominant risk factor for glioma and revealed strong interactions among ionizing radiation exposure, PARP1 A762V, MGMT F84L, and APEX1 E148D. Interestingly, the risk for glioma was dramatically increased in ionizing radiation exposure individuals who had the wild-type genotypes of MGMT F84L and PARP1 A762V (adjusted odds ratios, 5.95; 95% confidence intervals, 2.21-16.65). Taken together, these results suggest that polymorphisms in DNA repair genes may act individually or together to contribute to glioma risk.

    View details for DOI 10.1158/1055-9965.EPI-08-0632

    View details for Web of Science ID 000262424200026

    View details for PubMedID 19124499

    View details for PubMedCentralID PMC2917049

  • Polymorphisms in the Interleukin-4 Receptor Gene are Associated with Better Survival in Patients with Glioblastoma CLINICAL CANCER RESEARCH Scheurer, M. E., Arnirian, E., Cao, Y., Gilbert, M. R., Aldape, K. D., Kornguth, D. G., El-Zein, R., Bondy, M. L. 2008; 14 (20): 6640–46

    Abstract

    Previous literature provides some evidence that atopic diseases, IgE levels, and inflammatory gene polymorphisms may be associated with risk of glioblastoma. The purpose of this study was to investigate the effects of certain inflammatory gene single nucleotide polymorphisms (SNP) on patient survival. Malignant gliomas are the most common type of primary brain tumor in adults, however, few prognostic factors have been identified.Using 694 incident adult glioma cases identified between 2001 and 2006 in Harris County, TX, we examined seven SNPs in the interleukin (IL)-4, IL-13, and IL-4 receptor (IL4R) genes. Cox proportional hazards regression was used to examine the association between the SNPs and overall and long-term survival, controlling for age at diagnosis, time between diagnosis and registration, extent of surgical resection, radiation therapy, and chemotherapy.We found that among high-grade glioma cases, IL4R rs1805016 (TT versus GT/GG) was significantly protective against mortality over time [hazard ratios (HR), 0.59; 95% confidence intervals (CI), 0.40-0.88]. The IL4R rs1805016 and rs1805015 TT genotypes were both found to be significantly associated with survival beyond 1 year among patients with high-grade glioma (HR, 0.44; 95% CI, 0.27-0.73 and HR, 0.63; 95% CI, 0.44-0.91, respectively). Furthermore, the IL4R haplotype analysis showed that SNPs in the IL4R gene may be interacting to affect long-term survival among high-grade glioma cases.These findings indicate that polymorphisms in inflammation pathway genes may play an important role in glioma survival. Further research on the effects of these polymorphisms on glioma prognosis is warranted.

    View details for DOI 10.1158/1078-0432.CCR-07-4681

    View details for Web of Science ID 000260359600035

    View details for PubMedID 18927306

    View details for PubMedCentralID PMC2995250

  • A COLLABORATIVE STUDY OF THE EPIDEMIOLOGY OF OLIGODENDROGLIAL TUMORS Mccarthy, B., Aldape, K., Bondy, M., Butler, M., Inskip, P., Ruder, A., Wrensch, M., Davis, F. OXFORD UNIV PRESS INC. 2008: 779
  • Association between hepatitis B virus and pancreatic cancer JOURNAL OF CLINICAL ONCOLOGY Hassan, M. M., Li, D., El-Deeb, A. S., Wolff, R. A., Bondy, M. L., Davila, M., Abbruzzese, J. L. 2008; 26 (28): 4557–62

    Abstract

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) are considered to be hepatotropic and are a major cause of hepatocellular carcinoma. However, little is known about the role of HBV and HCV infection in other malignancies. This study aimed to determine whether HBV and HCV infections increase the risk for pancreatic cancer development.At The University of Texas M. D. Anderson Cancer Center, Houston, TX, we recruited 476 patients with pathologically confirmed adenocarcinoma of the pancreas and 879 age-, sex-, and race-matched healthy controls. Blood samples were tested for the presence of HCV antibodies (anti-HCV), HBV surface antigen (HBsAg), antibodies against HBV core antigen (anti-HBc), and antibodies against HBsAg (anti-HBs). The positive samples were retested by two confirmatory tests. An unconditional multivariable logistic regression analysis was used to estimate adjusted odds ratios (AORs).Anti-HCV was positive in seven cases (1.5%) and nine controls (1%). Anti-HBc was positive in 36 cases (7.6%) and 28 controls (3.2%). The estimated AORs and 95% CIs were as follows: anti-HCV-positive, 0.9 (95% CI, 0.3 to 2.8), anti-HBc-positive, 2.5 (95% CI, 1.5 to 4.2), anti-HBc-positive/anti-HBs-positive, 2.3 (95% CI, 1.2 to 4.2), and anti-HBc-positive/anti-HBs-negative, 4 (95% CI, 1.4 to 11.1). Risk modification by past exposure to HBV was observed among diabetics (AOR, 7.1; 95% CI, 1.7 to 28.7).Past exposure to HBV may be associated with pancreatic cancer development. Should such findings be confirmed by other studies, it may offer important insights into the etiology of pancreatic cancer and may suggest the need to consider prevention of HBV reactivation among patients with HBV-related pancreatic cancer during chemotherapy.

    View details for DOI 10.1200/JCO.2008.17.3526

    View details for Web of Science ID 000259648300010

    View details for PubMedID 18824707

    View details for PubMedCentralID PMC2562875

  • PROGNOSTIC FACTORS IN ADULT AND PEDIATRIC EPENDYMOMA Amirian, E., Scheurer, M., Armstrong, T., Bondy, M., Gilbert, M. OXFORD UNIV PRESS INC. 2008: 780–81
  • Correlates of susceptibility to smoking among Mexican origin youth residing in Houston, Texas: A cross-sectional analysis BMC PUBLIC HEALTH Wilkinson, A. V., Waters, A. J., Vasudevan, V., Bondy, M. L., Prokhorov, A. V., Spitz, M. R. 2008; 8: 337

    Abstract

    Survey data suggest that in Texas Latino youth exhibit higher rates of susceptibility to smoking than youth from other ethnic groups. In this analysis we examined the relationship between susceptibility to smoking and well-known risk factors associated with smoking initiation among a cohort of 11 to 13 year old Mexican origin youth residing in Houston, Texas.We analyzed cross-sectional survey data from 1,187 participants who reported they had never smoked, even a puff of a cigarette. The survey assessed peer and family social influence, school and neighborhood characteristics, level of family acculturation and socioeconomic status, and attitudes toward smoking. Bivariate associations, Student's t-tests, and logistic regression analysis were used to examine predictors of susceptibility.Overall, 22.1% of the never-smokers were susceptible to smoking. Boys were more likely to be susceptible than girls (25.6% vs. 18.9%), and susceptible children were slightly older than non-susceptible children (12.1 vs. 11.8 years). In addition, multivariate analyses revealed that positive expectations about smoking exerted the strongest influence on susceptibility status (odds ratio = 4.85). Multivariate analyses further revealed that compared to non-susceptible participants, susceptibles were more likely to report peer influences supportive of smoking, lower subjective social status and more detentions at school, more temptations to try smoking and to have a mother and a brother who smokes.Our findings suggest that interventions that target positive expectations about smoking may be useful in this population. Furthermore, because youth encounter smoking-initiation risk factors in different social environments, our results underscore the continued need for both family- and school-based primary prevention programs to adequately combat their influence. The results also can be used to inform the development of culturally sensitive programs for Mexican origin youth.

    View details for DOI 10.1186/1471-2458-8-337

    View details for Web of Science ID 000260300000001

    View details for PubMedID 18822130

    View details for PubMedCentralID PMC2569937

  • Relationship between obesity and pathologic response to neoadjuvant chemotherapy among women with operable breast cancer Litton, J. K., Gonzalez-Angulo, A. M., Warneke, C. L., Buzdar, A. U., Kau, S., Bondy, M., Mahabir, S., Hortobagyi, G. N., Brewster, A. M. AMER SOC CLINICAL ONCOLOGY. 2008: 4072–77

    Abstract

    To understand the mechanism through which obesity in breast cancer patients is associated with poorer outcome, we evaluated body mass index (BMI) and response to neoadjuvant chemotherapy (NC) in women with operable breast cancer.From May 1990 to July 2004, 1,169 patients were diagnosed with invasive breast cancer at M. D. Anderson Cancer Center and received NC before surgery. Patients were categorized as obese (BMI >or= 30 kg/m(2)), overweight (BMI of 25 to < 30 kg/m(2)), or normal/underweight (BMI < 25 kg/m(2)). Logistic regression was used to examine associations between BMI and pathologic complete response (pCR). Breast cancer-specific, progression-free, and overall survival times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. All statistical tests were two-sided.Median age was 50 years; 30% of patients were obese, 32% were overweight, and 38% were normal or underweight. In multivariate analysis, there was no significant difference in pCR for obese compared with normal weight patients (odds ratio [OR] = 0.78; 95% CI, 0.49 to 1.26). Overweight and the combination of overweight and obese patients were significantly less likely to have a pCR (OR = 0.59; 95% CI, 0.37 to 0.95; and OR = 0.67; 95% CI, 0.45 to 0.99, respectively). Obese patients were more likely to have hormone-negative tumors (P < .01), stage III tumors (P < .01), and worse overall survival (P = .006) at a median follow-up time of 4.1 years.Higher BMI was associated with worse pCR to NC. In addition, its association with worse overall survival suggests that greater attention should be focused on this risk factor to optimize the care of breast cancer patients.

    View details for DOI 10.1200/JCO.2007.14.4527

    View details for Web of Science ID 000259350200004

    View details for PubMedID 18757321

    View details for PubMedCentralID PMC6557586

  • Residual risk of breast cancer recurrence 5 years after adjuvant therapy JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Brewster, A. M., Hortobagyi, G. N., Broglio, K. R., Kau, S., Santa-Maria, C. A., Arun, B., Buzdar, A. U., Booser, D. J., Valero, V., Bondy, M., Esteva, F. J. 2008; 100 (16): 1179–83

    Abstract

    There is limited prognostic information to identify breast cancer patients who are at risk for late recurrences after adjuvant or neoadjuvant systemic therapy (AST). We evaluated the residual risk of recurrence and prognostic factors of 2838 patients with stage I-III breast cancer who were treated with AST between January 1, 1985, and November 1, 2001, and remained disease free for 5 years. Residual recurrence-free survival was estimated from the landmark of 5 years after AST to date of first recurrence or last follow-up using the Kaplan-Meier method. The log-rank test (two-sided) was used to compare groups. Residual recurrence-free survival rates at 5 and 10 years were 89% and 80%, respectively, and 216 patients developed a recurrence event. The 5-year residual risks of recurrence for patients with stage I, II, and III cancers were 7% (95% confidence interval [CI] = 3% to 15%), 11% (95% CI = 9% to 13%), and 13% (95% CI = 10% to 17%), respectively (P = .02). In multivariable analysis, stage, grade, hormone receptor status, and endocrine therapy were associated with late recurrences. Breast cancer patients have a substantial residual risk of recurrence, and selected tumor characteristics are associated with late recurrences.

    View details for DOI 10.1093/jnci/djn233

    View details for Web of Science ID 000258913600011

    View details for PubMedID 18695137

    View details for PubMedCentralID PMC6592411

  • Genetic variants in the H2AFX promoter region are associated with risk of sporadic breast cancer in non-Hispanic white women aged <= 55 years BREAST CANCER RESEARCH AND TREATMENT Lu, J., Wei, Q., Bondy, M. L., Brewster, A. M., Bevers, T. B., Yu, T., Buchholz, T. A., Meric-Bernstam, F., Hunt, K. K., Singletary, S., Wang, L. 2008; 110 (2): 357–66

    Abstract

    The histone protein family member X (H2AFX) is important in maintaining chromatin structure and genetic stability. Genetic variants in H2AFX may alter protein functions and thus cancer risk. In this case-control study, we genotyped four common single nucleotide polymorphisms (i.e., -1654A > G [rs643788], -1420G > A [rs8551], and -1187T > C [rs7759] in the H2AFX promoter region and 1057C > T [rs7350] in the 3' untranslated region (UTR)) in 467 patients with sporadic breast cancer and 488 cancer-free controls. All female subjects were non-Hispanic whites aged T polymorphism. Therefore, we believe that H2AFX promoter polymorphisms may contribute to the etiology of sporadic breast cancer in young non-Hispanic white women. Larger association studies and related functional studies are warranted to confirm these findings.

    View details for DOI 10.1007/s10549-007-9717-2

    View details for Web of Science ID 000256471100018

    View details for PubMedID 17851762

    View details for PubMedCentralID PMC3030478

  • Detection of human cytomegalovirus in different histological types of gliomas ACTA NEUROPATHOLOGICA Scheurer, M. E., Bondy, M. L., Aldape, K. D., Albrecht, T., El-Zein, R. 2008; 116 (1): 79–86

    Abstract

    The association between human cytomegalovirus (HCMV) infection and glioblastoma has been a source of debate in recent years because of conflicting laboratory reports concerning the presence of the virus in glioma tissue. HCMV is a ubiquitous herpesvirus that exhibits tropism for glial cells and has been shown to transform cells in vitro. Using sensitive immunohistochemical and in situ hybridization methods in 50 glioma samples, we detected HCMV antigen and DNA in 21/21 cases of glioblastoma, 9/12 cases of anaplastic gliomas and 14/17 cases of low-grade gliomas. Reactivity against the HCMV IE1 antigen (72 kDa) exhibited histology-specific patterns with more nuclear staining for anaplastic and low-grade gliomas, while GBMs showed nuclear and cytoplasmic staining that likely occurs with latent infection. Using IHC, the number of HCMV-positive cells in GBMs was 79% compared to 48% in lower grade tumors. Non-tumor areas of the tissue contained only four and 1% of HCMV-positive cells for GBMs and lower grade tumors, respectively. Hybridization to HCMV DNA in infected cells corresponded to patterns of immunoreactivity. Our findings support previous reports of the presence of HCMV infection in glioma tissues and advocate optimization of laboratory methods for the detection of active HCMV infections. This will allow for detection of low-level latent infections that may play an important role in the initiation and/or promotion of malignant gliomas.

    View details for DOI 10.1007/s00401-008-0359-1

    View details for Web of Science ID 000257544200008

    View details for PubMedID 18351367

    View details for PubMedCentralID PMC3001277

  • Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer CARCINOGENESIS Suzuki, H., Morris, J. S., Li, Y., Doll, M. A., Hein, D. W., Liu, J., Jiao, L., Hassan, M. M., Day, R. S., Bondy, M. L., Abbruzzese, J. L., Li, D. 2008; 29 (6): 1184–91

    Abstract

    Aromatic amines, N-nitroso compounds and heterocyclic amines are suspected human pancreatic carcinogens. Cytochrome P450 (CYP) 1A2, N-acetyltransferase (NAT) 1, NAT2 and sulfotransferase (SULT) are enzymes involved in the metabolism of these carcinogens. To test the hypothesis that genetic variations in carcinogen metabolism modify the risk of pancreatic cancer (PC), we investigated the effect of single-nucleotide polymorphisms (SNPs) of the CYP1A2, NAT1, NAT2 and SULT1A1 gene on modification of the risk of PC in a hospital-based study of 755 patients with pancreatic adenocarcinoma and 636 healthy frequency-matched controls. Smoking and dietary mutagen exposure information was collected by personal interviews. Genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism and Taqman methods. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional multivariate logistic regression analysis. We observed no significant main effects of any of these genes on the risk of PC. The CYP1A2 and NAT1 but not SULT1A1 and NAT2 genotypes showed significant interactions with heavy smoking in women not men. In contrast, a significant interaction between NAT1 genotype and dietary mutagen intake on modifying the risk of PC were observed among men but not women. The OR (95% CI) of PC was 2.23 (1.33-3.72) and 2.54 (1.51-4.25) for men having the NAT1*10 and a higher intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and benzo[a]pyrene, respectively, compared with individuals having no NAT1*10 or a lower intake of these dietary mutagens. These data suggest the existence of gender-specific susceptibility to tobacco carcinogen and dietary mutagen exposure in PC.

    View details for DOI 10.1093/carcin/bgn085

    View details for Web of Science ID 000257398100014

    View details for PubMedID 18499698

    View details for PubMedCentralID PMC2443278

  • An analysis of prognostic factors in pediatric posterior fossa ependymomas: Challenges in the study of prognostic factors in childhood brain tumors and a plea for a novel approach Tihan, T., Morgan, L., Buffler, P., Bondy, M., Mckean-Cowdin, R., Wrensch, M. DUKE UNIV PRESS. 2008: 411
  • Challenges to epidemiology studies of brain tumors (report from the brain tumor epidemiology consortium [BTEC]) Bondy, M. DUKE UNIV PRESS. 2008: 411–12
  • Inflammation gene polymorphisms associated with glioma risk Amirian, E., Scheurer, M. E., Ei-Zein, R., Bondy, M. L. OXFORD UNIV PRESS INC. 2008: S64
  • Pharmacoepidemiology of myelotoxicity (TOX) with temozolomide (TMZ) in malignant glioma patients Armstrong, T. S., Cao, Y., Vera, E., Scheurer, M. E., Manning, R., Okcu, M. F., Bondy, M., Gilbert, M. R. AMER SOC CLINICAL ONCOLOGY. 2008
  • Long-term anti-inflammatory and antihistamine medication use and adult glioma risk CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Scheurer, M. E., El-Zein, R., Thompson, P. A., Aldape, K. D., Levin, V. A., Gilbert, M. R., Weinberg, J. S., Bondy, M. L. 2008; 17 (5): 1277–81

    Abstract

    A personal history of asthma or allergy has been associated with a reduced risk for adult malignant gliomas. Recent reports on the use of nonsteroidal anti-inflammatory drugs (NSAID) and the presence of risk alleles in asthma susceptibility genes showed similar inverse associations. To further explore the relationship between immune mediators and gliomas, we examined the use of NSAID and antihistamines, history of asthma or allergy, and infection in 325 glioma cases and 600 frequency-matched controls from the metropolitan area of Houston, TX (2001-2006). The regular use of NSAID was associated with a 33% reduction in the risk for glioma, suggestive of possible antitumor activity. Surprisingly, regular long-term antihistamine use among those reporting a history of asthma or allergies was significantly associated with a 3.5-fold increase in the risk for glioma. Similar to previous reports, cases in our study were less likely to have reported asthma, allergy, or a history of a number of viral infections (chickenpox or shingles, oral herpes, and mononucleosis) than controls. We therefore speculate that the observed positive association with antihistamine use may reflect an alteration of protective immune factors in susceptible individuals. Our results lend additional support for an important but unknown link between malignant brain tumors and immune mediators.

    View details for DOI 10.1158/1055-9965.EPI-07-2621

    View details for Web of Science ID 000256012800036

    View details for PubMedID 18483351

    View details for PubMedCentralID PMC6436627

  • Issues of diagnostic review in brain tumor studies: From the brain tumor epidemiology consortium CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Davis, F. G., Malmer, B. S., Aldape, K., Barnholtz-Sloan, J. S., Bondy, M. L., Brannstrom, T., Bruner, J. M., Burger, P. C., Collins, V., Inskip, P. D., Kruchko, C., McCarthy, B. J., McLendon, R. E., Sadetzki, S., Tihan, T., Wrensch, M. R., Buffler, P. A. 2008; 17 (3): 484–89

    Abstract

    Epidemiologists routinely conduct centralized single pathology reviews to minimize interobserver diagnostic variability, but this practice does not facilitate the combination of studies across geographic regions and institutions where diagnostic practices differ. A meeting of neuropathologists and epidemiologists focused on brain tumor classification issues in the context of protocol needs for consortial studies (http://epi.grants.cancer.gov/btec/). It resulted in recommendations relevant to brain tumors and possibly other rare disease studies. Two categories of brain tumors have enough general agreement over time, across regions, and between individual pathologists that one can consider using existing diagnostic data without further review: glioblastomas and meningiomas (as long as uniform guidelines such as those provided by the WHO are used). Prospective studies of these tumors benefit from collection of pathology reports, at a minimum recording the pathology department and classification system used in the diagnosis. Other brain tumors, such as oligodendroglioma, are less distinct and require careful histopathologic review for consistent classification across study centers. Epidemiologic study protocols must consider the study specific aims, diagnostic changes that have taken place over time, and other issues unique to the type(s) of tumor being studied. As diagnostic changes are being made rapidly, there are no readily available answers on disease classification issues. It is essential that epidemiologists and neuropathologists collaborate to develop appropriate study designs and protocols for specific hypothesis and populations.

    View details for DOI 10.1158/1055-9965.EPI-07-0725

    View details for Web of Science ID 000254373600005

    View details for PubMedID 18349266

  • XRCC2 and XRCC3 gene polymorphism and risk of pancreatic cancer AMERICAN JOURNAL OF GASTROENTEROLOGY Jiao, L., Hassan, M. M., Bondy, M. L., Wolff, R. A., Evans, D. B., Abbruzzese, J. L., Li, D. 2008; 103 (2): 360–67

    Abstract

    XRCC2 and XRCC3 are key components of the homologous recombination (HR) machinery that repairs DNA double-strand breaks. We hypothesized that the altered HR repair capacity conferred by single nucleotide polymorphisms (SNPs) would modify individual susceptibility to sporadic pancreatic cancer.In a hospital-based case-control study, genomic DNA and exposure information was obtained from 468 patients with pathologically confirmed pancreatic adenocarcinoma and 498 frequency-matched healthy controls at M.D. Anderson Cancer Center during January 2000 to September 2006. Genotypes of XRCC2 31479 G>A (Arg188His) and XRCC3 17893 A>G and 18067 C>T (Thr241Met) were determined using the Masscode technology. Unconditional logistic regression models were used to estimate the odds ratio (OR) and its 95% confidence interval (CI) in non-Hispanic whites (408 cases and 449 controls).The distribution of genotype frequencies was not different between cases and controls. We observed a significant effect modification between XRCC2 polymorphism and smoking status and pack-year of smoking in modifying pancreatic cancer risk (P value for interaction 0.02 and 0.05, respectively). Compared with never-smokers carrying the XRCC2 Arg188Arg genotype, the OR (95% CI) for individuals carrying the (188)His allele was 2.32 (1.25-4.31) among ever-smokers, 1.43 (0.59-3.48) among light smokers (< or = 22 pack-years), and 3.42 (1.47-7.96) among heavy smokers (> or =22 pack-years). The two XRCC3 SNPs are in strong linkage disequilibrium, but there was no suggestive association between XRCC3 genotype and the risk of pancreatic cancer.XRCC2 Arg188His polymorphism may be one of the genetic modifiers for smoking-related pancreatic cancer.

    View details for DOI 10.1111/j.1572-0241.2007.01615.x

    View details for Web of Science ID 000253049700016

    View details for PubMedID 17986315

    View details for PubMedCentralID PMC2268638

  • Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium. Cancer Bondy, M. L., Scheurer, M. E., Malmer, B., Barnholtz-Sloan, J. S., Davis, F. G., Il'yasova, D., Kruchko, C., McCarthy, B. J., Rajaraman, P., Schwartzbaum, J. A., Sadetzki, S., Schlehofer, B., Tihan, T., Wiemels, J. L., Wrensch, M., Buffler, P. A. 2008; 113 (7 Suppl): 1953–68

    Abstract

    Epidemiologists in the Brain Tumor Epidemiology Consortium (BTEC) have prioritized areas for further research. Although many risk factors have been examined over the past several decades, there are few consistent findings, possibly because of small sample sizes in individual studies and differences between studies in patients, tumor types, and methods of classification. Individual studies generally have lacked samples of sufficient size to examine interactions. A major priority based on available evidence and technologies includes expanding research in genetics and molecular epidemiology of brain tumors. BTEC has taken an active role in promoting understudied groups, such as pediatric brain tumors; the etiology of rare glioma subtypes, such as oligodendroglioma; and meningioma, which, although it is not uncommon, has only recently been registered systematically in the United States. There also is a pressing need for more researchers, especially junior investigators, to study brain tumor epidemiology. However, relatively poor funding for brain tumor research has made it difficult to encourage careers in this area. In this report, BTEC epidemiologists reviewed the group's consensus on the current state of scientific findings, and they present a consensus on research priorities to identify which important areas the science should move to address.

    View details for DOI 10.1002/cncr.23741

    View details for PubMedID 18798534

    View details for PubMedCentralID PMC2861559

  • Clinicopathologic characteristics and prognostic factors in 420 metastatic breast cancer patients with central nervous system metastasis CANCER Altundag, K., Bondy, M. L., Mirza, N. Q., Kau, S., Broglio, K., Hortobagyi, G. N., Rivera, E. 2007; 110 (12): 2640–47

    Abstract

    Breast cancer is the second most common cause of central nervous system (CNS) metastases. Several risk factors for CNS metastases have been reported. The objective of the current study was to describe clinicopathologic characteristics and prognostic factors in breast cancer patients with CNS metastases.The authors retrospectively evaluated clinical data from 420 patients who had been diagnosed with breast cancer and CNS metastasis between 1994 and 2004 at the University of Texas M. D. Anderson Cancer Center.The median age of the patients at the time of diagnosis of breast cancer was 45 years (range, 25-77 years). Premenopausal and postmenopausal patients were distributed equally. Most patients had invasive ductal histology (91.2%), grade 3 tumors (81.4%) (using the modified Black nuclear grading system), T2 tumor classification (40.1%), and N1 lymph node status (59.7%) diagnosis. Forty percent of patients had estrogen receptor (ER)-positive disease, and 34% had progesterone receptor-positive disease. HER-2/neu status was recorded for only 248 patients, and 39% of the patients in that group had HER-2/neu-positive disease. The most common sites of first metastasis were liver, bone, and lung. CNS metastasis was the site of first recurrence in 53 patients (12%). In total, 329 patients had received either neoadjuvant treatment (113 patients) or adjuvant chemotherapy (216 patients). The majority of those patients (74.4%) had received anthracycline-based regimens. Metastasis was solitary in 111 patients (26.4%), and 29 patients had only leptomeningeal metastases. The median time from breast cancer diagnosis to CNS metastasis was 30.9 months (range, from -5 months to 216.7 months). The median follow-up after a diagnosis of CNS metastasis was 6 months (range, 7-95.9 months). In all, 359 patients died, and the overall median survival was 6.8 months. Only age at diagnosis and ER status were associated significantly with overall survival in the multivariate analysis.The current results indicated that the prognosis remains patients with breast cancer metastatic to the CNS. More effective treatment approaches are needed for patients with CNS metastases, even for those with favorable prognostic factors, such as ER-positive tumors or younger age.

    View details for DOI 10.1002/cncr.23088

    View details for Web of Science ID 000251573600006

    View details for PubMedID 17960791

  • Projecting individualized absolute invasive breast cancer risk in African American women JOURNAL OF THE NATIONAL CANCER INSTITUTE Gail, M. H., Costantino, J. P., Pee, D., Bondy, M., Newman, L., Selvan, M., Anderson, G. L., Malone, K. E., Marchbanks, P. A., McCaskill-Stevens, W., Norman, S. A., Simon, M. S., Spirtas, R., Ursin, G., Bernstein, L. 2007; 99 (23): 1782–92

    Abstract

    The Breast Cancer Risk Assessment Tool of the National Cancer Institute (NCI) is widely used for counseling and determining eligibility for breast cancer prevention trials, although its validity for projecting risk in African American women is uncertain. We developed a model for projecting absolute risk of invasive breast cancer in African American women and compared its projections with those from the Breast Cancer Risk Assessment Tool.Data from 1607 African American women with invasive breast cancer and 1647 African American control subjects in the Women's Contraceptive and Reproductive Experiences (CARE) Study were used to compute relative and attributable risks that were based on age at menarche, number of affected mother or sisters, and number of previous benign biopsy examinations. Absolute risks were obtained by combining this information with data on invasive breast cancer incidence in African American women from the NCI's Surveillance, Epidemiology and End Results Program and with national mortality data. Eligibility screening data from the Study of Tamoxifen and Raloxifene (STAR) trial were used to determine how the new model would affect eligibility, and independent data from the Women's Health Initiative (WHI) were used to assess how well numbers of invasive breast cancers predicted by the new model agreed with observed cancers.Tables and graphs for estimating relative risks and projecting absolute invasive breast cancer risk with confidence intervals were developed for African American women. Relative risks for family history and number of biopsies and attributable risks estimated from the CARE population were lower than those from the Breast Cancer Risk Assessment Tool, as was the discriminatory accuracy (i.e., concordance). Using eligibility screening data from the STAR trial, we estimated that 30.3% of African American women would have had 5-year invasive breast cancer risks of at least 1.66% by use of the CARE model, compared with only 14.5% by use of the Breast Cancer Risk Assessment Tool. The numbers of cancers predicted by the CARE model agreed well with observed numbers of cancers (i.e., it was well calibrated) in data from the WHI, except that it underestimated risk in African American women with breast biopsy examinations.The CARE model usually gave higher risk estimates for African American women than the Breast Cancer Risk Assessment Tool and is recommended for counseling African American women regarding their risk of breast cancer.

    View details for DOI 10.1093/jnci/djm223

    View details for Web of Science ID 000251545600010

    View details for PubMedID 18042936

  • Risk factors for pancreatic cancer: Case-control study AMERICAN JOURNAL OF GASTROENTEROLOGY Hassan, M. M., Bondy, M. L., Wolff, R. A., Abbruzzese, J. L., Vauthey, J., Pisters, P. W., Evans, D. B., Khan, R., Chou, T., Lenzi, R., Jiao, L., Li, D. 2007; 102 (12): 2696–2707

    Abstract

    Although cigarette smoking is the most well-established environmental risk factor for pancreatic cancer, the interaction between smoking and other risk factors has not been assessed. We evaluated the independent effects of multiple risk factors for pancreatic cancer and determined whether the magnitude of cigarette smoking was modified by other risk factors in men and women.We conducted a hospital-based case-control study involving 808 patients with pathologically diagnosed pancreatic cancer and 808 healthy frequency-matched controls. Information on risk factors was collected by personal interview, and unconditional logistic regression was used to determine adjusted odds ratios (AORs) by the maximum-likelihood method.Cigarette smoking, family history of pancreatic cancer, heavy alcohol consumption (>60 mL ethanol/day), diabetes mellitus, and history of pancreatitis were significant risk factors for pancreatic cancer. We found synergistic interactions between cigarette smoking and family history of pancreatic cancer (AOR 12.8, 95% confidence interval [CI] 1.6-108.9) and diabetes mellitus (AOR 9.3, 95% CI 2.0-44.1) in women, according to an additive model. Approximately 23%, 9%, 3%, and 5% of pancreatic cancer cases in this study were related to cigarette smoking, diabetes mellitus, heavy alcohol consumption, and family history of pancreatic cancer, respectively.The significant synergy between these risk factors suggests a common pathway for carcinogenesis of the pancreas. Determining the underlying mechanisms for such synergies may lead to the development of pancreatic cancer prevention strategies for high-risk individuals.

    View details for DOI 10.1111/j.1572-0241.2007.01510.x

    View details for Web of Science ID 000251249300015

    View details for PubMedID 17764494

    View details for PubMedCentralID PMC2423805

  • Aggregation of cancer in first-degree relatives of patients with glioma CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Scheurer, M. E., Etzel, C. J., Liu, M., El-Zein, R., Airewele, G. E., Malmer, B., Aldape, K. D., Weinberg, J. S., Yung, W., Bondy, M. L. 2007; 16 (11): 2491–95

    Abstract

    Previous studies have been inconclusive in estimating the risk of different cancer sites among close relatives of glioma patients; however, malignant melanoma has consistently been described.We obtained family history information from 1,476 glioma patients under age 75 years who registered at M. D. Anderson Cancer Center between June 1992 and June 2006. The number of observed cancers (N=1,001) among 8,746 first-degree relatives (FDR) was compared with the number expected from age-, sex-, and calendar year-specific rates from the Surveillance, Epidemiology, and End Results Program using standardized incidence ratios (SIR).The overall SIR for any cancer was 1.21 (95% confidence interval, 1.14-1.29). Among FDRs under 45 years the overall SIR was 5.08, and for relatives >45 years the overall SIR was 0.95. The SIRs were significantly elevated for brain tumors (2.14), melanoma (2.02), and sarcoma (3.83). We observed an excess of pancreatic cancer, which was significantly higher only among mothers.We observed an overall 21% increase in cancer among the FDRs of glioma patients including excess cases of brain tumors and melanoma, which could point to similar genetic contributions to these two malignancies. A large international linkage study is under way to examine potential genomic regions important for familial glioma.

    View details for DOI 10.1158/1055-9965.EPI-07-0576

    View details for Web of Science ID 000251123500045

    View details for PubMedID 18006942

    View details for PubMedCentralID PMC2995005

  • Factors associated with advanced disease stage at diagnosis in a population-based study of patients with newly diagnosed breast cancer AMERICAN JOURNAL OF EPIDEMIOLOGY Hahn, K. E., Bondy, M. L., Selvan, M., Lund, M., Liff, J. M., Flagg, E. W., Brinton, L. A., Porter, P., Eley, J., Coates, R. J. 2007; 166 (9): 1035–44

    Abstract

    Breast cancer is diagnosed at a younger age and a more advanced stage in African-American women than in White women. The authors investigated the effects of several factors, including race, on stage of breast cancer in women aged 20-54 years living in Atlanta, Georgia, and diagnosed between 1990 and 1992. A total of 251 African-American and 580 White women were interviewed and their medical records reviewed. By use of polytomous logistic regression, factors possibly influencing stage and racial differences in stage were studied. In African-American women, the odds of stage III/IV breast cancer at diagnosis were almost four times the odds in White women (odds ratio = 3.79, 95% confidence interval: 2.45, 5.89) and approximately two and one-half times for stage IIA or stage IIB disease (odds ratio = 2.57, 95% confidence interval: 1.66, 3.99; odds ratio = 1.94, 95% confidence interval: 1.31, 2.86, respectively). These racial differences appeared to be largely explained by insurance status, poverty, history of mammography, method of tumor detection, and obesity. Interventions targeting these factors could potentially lower the stage at diagnosis for African-American breast cancer patients and, in doing so, improve their survival and other outcomes.

    View details for DOI 10.1093/aje/kwm177

    View details for Web of Science ID 000250400700007

    View details for PubMedID 17690220

  • Haplotype of N-acetyltransferase 1 and 2 and risk of pancreatic cancer CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Jiao, L., Doll, M. A., Hein, D. W., Bondy, M. L., Hassan, M. M., Hixson, J. E., Abbruzzese, J. L., Li, D. 2007; 16 (11): 2379–86

    Abstract

    We examined the association between N-acetyltransferase 1 and 2 (NAT1 and NAT2) haplotype and risk of pancreatic cancer by genotyping eight NAT1 and seven NAT2 single nucleotide polymorphisms in 532 patients and in 581 healthy controls (all non-Hispanic white) who were recruited at M. D. Anderson Cancer Center from January 2000 to December 2006. Haplotypes were reconstructed by using an expectation-maximization algorithm. Odds ratios and 95% confidence intervals were estimated by using unconditional logistic regression models. Covariates included age (continuous variable), sex, pack-year of smoking (categorical), and history of diabetes when appropriate. NAT1 and NAT2 genotype was mutually adjusted. The prevalence of haplotype NAT1*10-NAT2*6A was 4.3% versus 2.7% (P=0.06) and NAT1*11-NAT2*6A was 1.2% versus 0.4% (P=0.05) in patients and controls, respectively. The diplotype NAT1*10/*10 or NAT1*10/*11 and NAT2*6A/any slow allele was associated with a higher risk of pancreatic cancer compared with other diplotypes (multivariate odds ratio, 4.15; 95% confidence interval, 1.15-15.00; P=0.03). NAT2 slow genotype were associated with increased risk of pancreatic cancer among heavy smokers and among individuals with a history of diabetes. We for the first time found that rare NAT1*10 or NAT1*11-NAT2*6A diplotype may be an "at-risk" genetic variant for pancreatic cancer. The NAT2*6A/any slow acetylation genotype may be a predisposing factor for pancreatic cancer among diabetics with smoking exposure. Our observations must be confirmed in larger independent studies.

    View details for DOI 10.1158/1055-9965.EPI-06-0992

    View details for Web of Science ID 000251123500030

    View details for PubMedID 18006927

    View details for PubMedCentralID PMC2215308

  • Polymorphisms in IL4R gene related to survival in glioma patients Scheurer, M., Amirian, E., Cao, Y., El-Zein, R., Levin, V. A., Bondy, M. DUKE UNIV PRESS. 2007: 480–81
  • Maternal BMI and country of birth as indicators of childhood obesity in children of Mexican origin OBESITY Hernandez-Valero, M. A., Wilkinson, A. V., Forman, M. R., Etzel, C. J., Cao, Y., Barcenas, C. H., Strom, S. S., Spitz, M. R., Bondy, M. L. 2007; 15 (10): 2512–19

    Abstract

    The goal of this study was to evaluate the relationship between maternal and childhood BMI at baseline in a group of 5- to 18-year-old children and their mothers, all of whom were of Mexican origin, low socioeconomic status, and enrolled in a cohort study in Houston, TX.Using data from 438 mother-child dyads residing in the same household, we completed logistic regression analyses to determine maternal factors associated with the child being overweight or at-risk-for-overweight, after adjusting for the child's gender, age, and level of physical activity and other maternal confounders.Almost one-half of the boys and girls (47% and 44%, respectively) were either overweight or at-risk-for-overweight. Obese mothers were twice as likely to have an overweight and/or at-risk-for-overweight child compared with normal-weight mothers. Women born in the U.S. were twice as likely to have an overweight and/or at-risk-for-overweight child compared with women born in Mexico. In addition, women with less than a high school education were twice as likely to have an overweight child compared with their more educated peers.The high prevalence of overweight or at-risk-for-overweight among Mexican-origin children of low socioeconomic status suggests a continued need to develop and implement culturally sensitive preventive interventions for this minority population. Our data also suggest a need to tailor such interventions particularly for children of obese mothers and those born in the U.S.

    View details for DOI 10.1038/oby.2007.298

    View details for Web of Science ID 000250377300018

    View details for PubMedID 17925478

  • Relationship between epidemiologic risk factors and breast cancer recurrence JOURNAL OF CLINICAL ONCOLOGY Brewster, A. M., Do, K., Thompson, P. A., Hahn, K. M., Sahin, A. A., Cao, Y., Stewart, M. M., Murray, J. L., Hortobagyi, G. N., Bondy, M. L. 2007; 25 (28): 4438–44

    Abstract

    Early-stage breast cancers are biologically heterogeneous and vary in clinical behavior, supporting the role of factors other than tumor size and lymph node involvement as outcome determinants. We evaluated the effect of epidemiologic breast cancer risk factors on recurrence in women with early-stage disease.Medical records from 2,327 women with early-stage breast cancer, treated at the M.D. Anderson Cancer Center between 1985 and 2000, were used to derive information on epidemiologic, clinical, and histological factors. Cox proportional hazards models were used to estimate the hazard ratios of 5-year risk of breast cancer recurrence adjusted for treatment and stage. Statistical tests were two-sided.None of the breast cancer risk factors were associated with recurrence, adjusting for tumor characteristics and treatment. A significant interaction between hormone replacement therapy (HRT) use and tumor hormone receptor status on risk of recurrence (P = .0003) was observed. Among ever-users of HRT, recurrence risk was two-fold lower for estrogen receptor (ER)--positive and progesterone receptor (PR)--positive tumors compared with ER- and PR-negative tumors; whereas, among never-users of HRT, there was no statistically significant association between recurrence risk and receptor status.HRT users who develop receptor-positive early-stage disease have better outcomes than those who develop receptor-negative disease. Among never-users of HRT, the expected beneficial effect of ER- or PR-positive tumors on recurrence risk was absent. These data lend support to the notion that the biology of hormone receptor-positive disease in HRT users differs from that in nonusers.

    View details for DOI 10.1200/JCO.2007.10.6815

    View details for Web of Science ID 000251073300018

    View details for PubMedID 17785707

    View details for PubMedCentralID PMC6559726

  • GLIOGENE - an international consortium to understand familial glioma CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Malmer, B., Adatto, P., Armstrong, G., Barnholtz-Sloan, J., Bernstein, J. L., Claus, E., Davis, F., Houlston, R., Il'yasova, D., Jenkins, R., Johansen, C., Lai, R., Lau, C., McCarthy, B., Nielsen, H., Olson, S. H., Sadetzki, S., Shete, S., Wiklund, F., Wrensch, M., Yang, P., Bondy, M. 2007; 16 (9): 1730–34

    Abstract

    Evidence for familial aggregation of glioma has been documented in both case-control and cohort studies and occurs apart from the well-described rare inherited genetic syndromes involving glioma: neurofibromatosis type 1 and 2, tuberous sclerosis, Turcot's syndrome, and Li-Fraumeni syndrome. Nonsyndromic glioma families have been studied but no genes have been identified in the two published linkage studies of familial glioma probably due to the small number of families. Because glioma is a rare but devastating cancer, and a family history of glioma has been observed in approximately 5% of the cases, we initiated an international consortium to identify glioma families not affected by syndromes to better understand the inherited factors related to this disease. The international consortium GLIOGENE is an acronym for "glioma gene" and includes 15 research groups in North America, Europe, and Israel to study familial glioma. The overarching goal is to characterize genes in glioma families using a genome-wide single-nucleotide polymorphism approach and conducting linkage analysis to identify new genomic regions or loci that could harbor genes important for gliomagenesis. Here, we review the rationale for studying familial glioma and our proposed strategy for the GLIOGENE study.

    View details for DOI 10.1158/1055-9965.EPI-07-0081

    View details for Web of Science ID 000249643600007

    View details for PubMedID 17855690

  • Incidence of pediatric melanoma in Texas: A report from the Texas Cancer Registry, 1995-2003 Spelman, A. R., Okcu, M. F., Bondy, M., Pappo, A. AMER SOC CLINICAL ONCOLOGY. 2007
  • Body mass index and response to neoadjuvant chemotherapy in breast cancer patients Litton, J. K., Gonzalez, A. M., Warneke, C. L., Kau, S., Buzdar, A. U., Bondy, M., Mahabir, S., Hortobagyi, G. N., Brewster, A. AMER SOC CLINICAL ONCOLOGY. 2007
  • Passive smoking and the use of noncigarette tobacco products in association with risk for pancreatic cancer: A case-control study CANCER Hassan, M. M., Abbruzzese, J. L., Bondy, M. L., Wolff, R. A., Vauthey, J., Pisters, P. W., Evans, D. B., Khan, R., Lenzi, R., Jiao, L., Li, D. 2007; 109 (12): 2547–56

    Abstract

    The associations between passive smoking and the use of noncigarette tobacco products with pancreatic cancer are not clear.In this case-control study, the authors collected information on passive smoking and the use of noncigarette tobacco products in 808 patients with pancreatic adenocarcinoma and 808 healthy controls by personal interview. Multivariable logistic regression was performed to estimate the adjusted odds ratio (AOR) and 95% confidence interval (95% CI).The results confirmed the previously reported association between active smoking and increased risk for pancreatic cancer. The AOR was 1.7 (95% CI, 1.4-2.2) for regular smokers, 1.8 (95% CI, 1.4-2.4) for long-term smokers, and 3.1 (95% CI, 2.2-4.3) for former smokers. Although passive smoking showed a nonsignificantly elevated risk for pancreatic cancer in the entire study population (AOR, 1.3; 95% CI, 0.9-1.7), the association was present among ever smokers (AOR, 1.7; 95% CI, 1.03-2.6) but was absent among never smokers (AOR, 1.1; 95% CI, 0.8-1.6). Neither intensity nor duration of passive smoking modified the risk of pancreatic cancer among never smokers. The use of chewing tobacco, snuff, and pipes showed no significant risk elevation for pancreatic cancer after controlling for the confounding effects of demographics and other known risk factors. The use of cigars in never smokers showed a borderline significant increase of risk for pancreatic cancer (AOR, 2.2; 95% CI, 1.0-4.7; P = .05).The current observations did not support a role for passive smoking or the use of noncigarette tobacco products in the etiology of pancreatic cancer. The association between cigar use and the risk of pancreatic cancer needs to be confirmed in other study populations.

    View details for DOI 10.1002/cncr.22724

    View details for Web of Science ID 000247113500021

    View details for PubMedID 17492688

    View details for PubMedCentralID PMC2215306

  • Birthplace, years of residence in the United States, and obesity among Mexican-American adults OBESITY Barcenas, C. H., Wilkinson, A. V., Strom, S. S., Cao, Y., Saunders, K. C., Mahabir, S., Hernandez-Valero, M. A., Forman, M. R., Spitz, M. R., Bondy, M. L. 2007; 15 (4): 1043–52

    Abstract

    To evaluate the association between birthplace (Mexico or U.S.) and obesity in men and women and to analyze the relationship between duration of U.S. residency and prevalence of obesity in Mexican immigrants.We used cross-sectional data from 7503 adults of Mexican descent residing in Harris County, TX, to evaluate the relationships among BMI, birthplace, and years of residency in the U.S., controlling for demographic characteristics, physical activity level, and acculturation level.U.S.-born adults had an increased risk (between 34% and 65%) of obesity compared with their Mexican-born counterparts. After controlling for recognized confounders and risk factors, this association was maintained in the highly acculturated only. Among highly acculturated obese U.S.-born men, 6% of the cases were attributable to the joint effect of birthplace and acculturation; in women, this proportion was 25%. Among Mexican-born women, there was an increasing trend in mean BMI with increasing duration of residency in the U.S.. Compared with immigrants who had lived in the U.S. for <5 years, Mexican-born women who had resided in the U.S. for >or=15 years had an adjusted BMI mean difference of 2.12 kg/m2 (95% confidence interval, 1.53-2.72).Mexican-born men and women have a lower risk of obesity than their U.S.-born counterparts, but length of U.S. residency among immigrants, especially in women, is directly associated with risk of obesity. Development of culturally specific interventions to prevent obesity in recent immigrants may have an important public health effect in this population.

    View details for DOI 10.1038/oby.2007.537

    View details for Web of Science ID 000245729300031

    View details for PubMedID 17426341

  • Dietary mutagen exposure and risk of pancreatic cancer CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Li, D., Day, R., Bondy, M. L., Sinha, R., Nguyen, N. T., Evans, D. B., Abbruzzese, J. L., Hassan, M. M. 2007; 16 (4): 655–61

    Abstract

    To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. A total of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (+/-5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases than controls showed a preference to well-done pork, bacon, grilled chicken, and pan-fried chicken, but not to hamburger and steak. Cases had a higher daily intake of food mutagens and mutagenicity activity (revertants per gram of daily meat intake) than controls did. The daily intakes of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP), as well as the mutagenic activity, were significant predictors for pancreatic cancer (P = 0.008, 0.031, and 0.029, respectively) with adjustment of other confounders. A significant trend of elevated cancer risk with increasing DiMeIQx intake was observed in quintile analysis (P(trend) = 0.024). A higher intake of dietary mutagens (those in the two top quintiles) was associated with a 2-fold increased risk of pancreatic cancer among those without a family history of cancer but not among those with a family history of cancer. A possible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to PhIP and BaP, P(interaction) = 0.09 and 0.099, respectively. These data support the hypothesis that dietary mutagen exposure alone and in interaction with other factors contribute to the development of pancreatic cancer.

    View details for DOI 10.1158/1055-9965.EPI-06-0993

    View details for Web of Science ID 000245732600004

    View details for PubMedID 17416754

    View details for PubMedCentralID PMC1892159

  • Glutathione S-transferase gene polymorphisms and risk and survival of pancreatic cancer CANCER Jiao, L., Bondy, M. L., Hassan, M. M., Chang, D. Z., Abbruzzese, J. L., Evans, D. B., Smolensky, M. H., Li, D. 2007; 109 (5): 840–48

    Abstract

    Pancreatic cancer is a multifactorial disease with metastasis-prone and therapy-resistant nature. The authors hypothesized that genetic variants of glutathione S-transferase (GST) affect detoxification of carcinogens and anticancer agents in the human pancreas and, thus, the risk and survival of pancreatic cancer.Genotypes of GSTM1, GSTT1, and GSTP1 were determined in 352 patients with pancreatic ductal adenocarcinoma and in a control group of 315 healthy, non-Hispanic whites (frequency-matched by age and sex). Survival analysis was performed in a subset of 290 patients. Epidemiological and clinical information was obtained. A multiple unconditional logistic regression model, a Cox proportional hazards model, and log-rank tests were used for statistical analysis.No significant main effects of any of 3 GST genes on the risk of pancreatic cancer were observed. Subgroup analysis showed that older individuals (aged >or=62 years) who carried the GSTP1*C ((105)Val-(114)Val) containing genotype tended to have a reduced risk compared with younger individuals who carried the non-*C genotype (for sex and pack-years of smoking, the adjusted odd ratio was 0.54; 95% confidence interval [95% CI], 0.29-1.02). In a survival analysis of 138 patients who received 5-flurorouracil, patients who carried the GSTP1*C containing genotype had a significantly longer survival than patients who carried the non-*C genotype (multivariate hazard ratio, 0.45; 95% CI, 0.22-0.94).The GSTP1*C variant conferred a possible protective effect against pancreatic cancer in older individuals and a significant survival advantage in patients who received 5-florouracil. The current findings must be confirmed before further inferences can be made.

    View details for DOI 10.1002/cncr.22468

    View details for Web of Science ID 000244582600004

    View details for PubMedID 17265526

    View details for PubMedCentralID PMC1892189

  • The XPD Asp(312) Asn and LyS(751)Gln polymorphisms, corresponding haplotype, and pancreatic cancer risk CANCER LETTERS Jiao, L., Hassan, M. M., Bondy, M. L., Abbruzzese, J. L., Evans, D. B., Li, D. 2007; 245 (1-2): 61–68

    Abstract

    We evaluated the association between the XPD exon 10 Asp(312)Asn and exon 23 Lys(751)Gln polymorphisms and the risk of pancreatic cancer in a hospital-based study of 344 patients and 386 controls frequency matched by age, gender, and race. Stratified analyses showed ever smokers carrying the Asn(312)Asn genotype had a significantly reduced risk when compared with those carrying the (312)Asp allele (OR=0.46, 95% confidence interval 0.24-0.88) (P for interaction=0.03). The (312)Asp-(751)Gln was identified as the putative at risk haplotype. Our study shows that the XPD gene polymorphism could be a genetic risk modifier for smoking-related pancreatic cancer.

    View details for DOI 10.1016/j.canlet.2005.12.026

    View details for Web of Science ID 000244146100007

    View details for PubMedID 16458430

    View details for PubMedCentralID PMC1741855

  • The emergence of networks in human genome epidemiology - Challenges and opportunities EPIDEMIOLOGY Seminara, D., Khoury, M. J., O'Brien, T. R., Manolio, T., Gwinn, M. L., Little, J., T Higgins, J. P., Bernstein, J. L., Boffetta, P., Bondy, M., Bray, M. S., Brenchley, P. E., Buffler, P. A., Casas, J. P., Chokkalingam, A. P., Danesh, J., Smith, G. D., Dolan, S., Duncan, R., Gruis, N. A., Hashibe, M., Hunter, D., Jarvelin, M., Malmer, B., Maraganore, D. M., Newton-Bishop, J. A., Riboli, E., Salanti, G., Taioli, E., Timpson, N., Uitterlinden, A. G., Vineis, P., Wareham, N., Winn, D. M., Zimmern, R., Ioannidis, J. P. 2007; 18 (1): 1-8
  • RE: "Lack of association of herpesviruses with brain tumors" JOURNAL OF NEUROVIROLOGY Scheurer, M. E., El-Zein, R., Bondy, M. L., Harkins, L., Cobbs, C. S. 2007; 13 (1): 85

    View details for DOI 10.1080/13550280601164325

    View details for Web of Science ID 000246064300012

    View details for PubMedID 17454453

  • Promoter polymorphism (-786T > C) in the endothelial nitric oxide synthase gene is associated with risk of sporadic breast cancer in non-Hispanic white women age younger than 55 years CANCER Lu, J., Wei, Q., Bondy, M. L., Yu, T., Li, D., Brewster, A., Shete, S., Sahin, A., Meric-Bernstam, F., Wang, L. 2006; 107 (9): 2245–53

    Abstract

    Nitric oxide (NO) is constitutively synthesized in the endothelium by endothelial nitric oxide synthase (eNOS) and acts as a pleiotropic regulator involved in carcinogenesis. Most breast cancers develop from mammary epithelial cells; therefore, NO may play a role in their development. It was hypothesized that eNOS polymorphisms are associated with risk of breast cancer.In the current hospital-based case-control study of 421 non-Hispanic white women with sporadic breast cancer and 423 frequency-matched control subjects, we genotyped 3 polymorphisms of eNOS (i.e., -786T>C, the 27-base pair [bp] variable number of tandem repeats [VNTR] in intron 4, and 894G>T [Glu298Asp]) and assessed their associations with risk of breast cancer.It was found that, compared with -786TT, the -786C variant genotypes were associated with a significantly increased risk of breast cancer in an allele dose-dependent manner (adjusted odds ratio [OR], 1.33 [95% confidence interval (95% CI)], 0.99-1.77 for -786TC; and OR, 1.79 [95% CI, 1.11-2.87] for -786CC; P(trend) = .007), but 27-bp VNTR and 894G>T genotypes were not. Stratification analysis demonstrated that the risk associated with -786C variant genotypes (-786TC/CC) was more pronounced in smokers and in those 50 years or older (OR, 1.82 [95% CI, 1.19-2.80] and OR, 2.08 [95% CI, 1.25-3.45], respectively), and in the estrogen and progesterone receptor-negative cases (OR, 1.70 [95% CI, 1.10-2.62] and OR, 1.57 [95% CI, 1.07-2.32], respectively). Furthermore, the C4G haplotype derived from the observed genotypes was also associated with a significantly increased risk of breast cancer (OR, 2.16; 95% CI, 1.07-4.36).The results suggest that eNOS polymorphisms (especially -786T>C) may play a role in the development of sporadic breast cancer.

    View details for DOI 10.1002/cncr.22269

    View details for Web of Science ID 000241777300019

    View details for PubMedID 17063466

  • Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women <= 55 years CARCINOGENESIS Lu, J., Wei, Q., Bondy, M. L., Li, D., Brewster, A., Shete, S., Yu, T., Sahin, A., Meric-Bernstam, F., Hunt, K. K., Singletary, S., Ross, M. I., Wang, L. 2006; 27 (11): 2209–16

    Abstract

    DNA double-strand breaks (DSBs) may lead to genomic instability and cancer if unrepaired. Nijmegen breakage syndrome 1 (NBS1) protein is one of the key proteins that participates in recognition and repair of DSBs in humans. We hypothesized that polymorphisms of NBS1 are associated with breast cancer risk. We selected three NBS1 haplotype-tagging polymorphisms (i.e. 924T>C, 8360G>C and 30537G>C) to represent all common (>or=5%) haplotypes reported in the National Institute of Environmental Health Sciences database and to reconstruct haplotypes. In a hospital-based case-control study of 421 non-Hispanic white patients with sporadic breast cancer (C polymorphism. Furthermore, the derived haplotypes were associated with risk in a dose-response manner as the number of variant (risk) alleles (i.e. 8360C, 924C or 30537C) increased (adjusted OR = 1.07, 95% CI = 0.78-1.46 for 1-2 variant alleles; adjusted OR = 2.47, 95% CI = 1.48-4.14 for 3-6 variant alleles; P(trend) = 0.006). These findings suggest that NBS1 polymorphisms and haplotypes may contribute to the etiology of sporadic breast cancer in young non-Hispanic white women. Large studies are warranted to confirm these findings.

    View details for DOI 10.1093/carcin/bgl077

    View details for Web of Science ID 000241629700008

    View details for PubMedID 16714331

  • Glutathione S-transferase polymorphisms are associated with survival in adults with who grade III glioma Kilburn, L. B., Okcu, M. F., Cao, Y., Renfro, A., Wang, L. E., Adatto, P., Gilbert, M., Aldape, K., Wei, Q., Bondy, M. DUKE UNIV PRESS. 2006: 459–60
  • Antihistamine and anti-inflammatory drug use associated differently for high-grade versus low-grade gliomas Scheurer, M. E., Wrensch, M., El-Zein, R. A., Moghadassi, M., Miike, R., Aldape, K. D., Bondy, M. L. DUKE UNIV PRESS. 2006: 408
  • Differing molecular pathology of pancreatic adenocarcinoma in Egyptian and United States patients INTERNATIONAL JOURNAL OF CANCER Soliman, A. S., Bondy, M., Webb, C., Schottenfeld, D., Bonner, J., El-Ghawalby, N., Soultan, A., Abdel-Wahab, M., Fathy, O., Ebidi, G., Zhang, Q., Greenson, J. K., Abbruzzese, J. L., Hamilton, S. R. 2006; 119 (6): 1455–61

    Abstract

    Variations in genetic mutations in pancreatic carcinoma between different populations have not been studied extensively, especially in developing countries where pancreatic cancer is rare. We studied the molecular pathology of 44 pancreatic carcinomas from patients residing in a heavily polluted region in the Nile River delta and compared the findings with tumors from 44 United States (US) patients. We evaluated K-ras mutations in codon 12, p53 mutations in exons 5-8, and Gadd45a mutations in exons 1 and 4. Overall, rates of K-ras, p53 and Gadd45 mutations were not statistically different in tumors of patients from Egypt and the US (67.4 vs. 63.4%; 27.3 vs. 36.4% and 9.1 vs. 4.5%, respectively). However, there were distinct differences in the specific types of K-ras and p53 mutations between the 2 groups. In K-ras, G --> T transversion mutation was more frequent in the tumors from Egypt than from the US (58.6 vs. 26.9%), whereas G --> C transversion was detected in 26.9% of US tumors but none from Egypt (p = 0.003). We also found a trend toward differences in the p53 exons in which mutations occurred, with higher frequency of exon 5 mutation and lower frequency of exon 6 mutation in Egyptian tumors. Logistic regression showed that K-ras G --> T transversion mutations and p53 exon 6 mutations were predicted by the country of residence of the patients. Our study identifies that there are differences in the types of mutations found in tumors from pancreatic carcinoma patients in Egypt and the US, and suggests that environmental factors may explain these differences.

    View details for DOI 10.1002/ijc.21986

    View details for Web of Science ID 000239877200033

    View details for PubMedID 16619252

  • Assessing breast cancer risk: Evolution of the Gail Model JOURNAL OF THE NATIONAL CANCER INSTITUTE Bondy, M. L., Newman, L. A. 2006; 98 (17): 1172–73

    View details for DOI 10.1093/jnci/djj365

    View details for Web of Science ID 000241721000002

    View details for PubMedID 16954464

  • Geographical clustering of pancreatic cancers in the northeast Nile Delta region of Egypt ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY Soliman, A. S., Wang, Stanley, J. D., El-Ghawalby, N., Bondy, M. L., Ezzat, F., Soultan, A., Abdel-Wahab, M., Fathy, O., Ebidi, G., Abdel-Karim, N., Do, K. A., Levin, B., Hamilton, Abbruzzese, J. L. 2006; 51 (1): 142–48

    Abstract

    The northeast Nile Delta, Egypt's most polluted region, appears to have a high incidence of pancreatic cancer. We sought to determine whether there is any geographic clustering of pancreatic cancers there and, if so, whether such clustering might be associated with environmental pollution. Using data from the medical records of the Gastrointestinal Surgical Center of Mansoura University in the Dakahleia Province of Egypt and detailed geographical maps of the northeast Nile Delta region, we plotted the residences of all 373 patients who had pancreatic cancer diagnosed between 1995 and 2000. The study region has 15 administrative districts, whose centroid coordinates, population, and number of pancreatic cancer patients were determined for this study. Monte Carlo simulation identified statistically significant clustering of pancreatic cancer in five subdivisions located near the Nile River and Delta plains. This clustering was independent of population size and formed two larger clusters. When data were analyzed by sex, clustering of pancreatic cancer was observed in the same five subdivisions for men but only two subdivisions showed clustering for women. Together, our data suggest that there is clustering of pancreatic cancer cases in the northeast Nile delta region and that this clustering may be related to water pollution. Our data also warrant future studies of the association between water pollution and pancreatic cancer in the region.

    View details for DOI 10.1007/s00244-005-0154-0

    View details for Web of Science ID 000236980500018

    View details for PubMedID 16453066

  • Premenopausal breast cancer and the association between estrogen receptor status, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and leptin. Eng-Wong, J., Chang, S., Hursting, S., Perkins, S. N., Nunez, N., Hill, H. L., Bondy, M., Li, D., Singletary, S. E. AMER SOC CLINICAL ONCOLOGY. 2006: 37S
  • Misclassification of Body Mass Index (BMI) using self-reported weight and height in an urban Mexican-American population. Saunders, K. C., Strom, S. S., Mahabir, S., Barcenas, C., Cao, Y., Spitz, M. R., Bondy, M. L. OXFORD UNIV PRESS INC. 2006: S223
  • Smoking susceptibility in Mexican origin youth: Family and community factors. Wilkinson, A. V., Barcenas, C. H., Saunders, K. C., Prokhorov, A. V., Bondy, M. L., Spitz, M. R. OXFORD UNIV PRESS INC. 2006: S66
  • Smoking susceptibility and experimentation with cigarettes among Mexican origin youth. Bondy, M. L., Prokhorov, A. V., Barcenas, C. H., Saunders, K. C., Wilkinson, A. V., Spitz, M. R. OXFORD UNIV PRESS INC. 2006: S138
  • Survival prediction in patients with glioblastoma multiforme by human telomerase genetic variation Wang, L., Wei, Q. Y., Wang, L. E., Aldape, K. D., Cao, Y. M., Okcu, M. F., Hess, K. R., El-Zein, R., Gilbert, M. R., Woo, S. Y., Prabhu, S. S., Fuller, G. N., Bondy, M. L. AMER SOC CLINICAL ONCOLOGY. 2006: 1627–32

    Abstract

    Glioblastoma multiforme (GBM) is the most common and aggressive glioma with the poorest survival. Use of biomarkers for screening patients with GBM may be used to modify treatments and improve outcomes. The level of human telomerase (hTERT) expression is an independent predictor of outcome of many cancers, and a functional variant of hTERT MNS16A (shorter tandem repeats or short [S] allele) is associated with increased hTERT mRNA expression. We investigated whether hTERT MNS16A variant genotype predicted survival in GBM patients.We genotyped hTERT MNS16A in 299 GBM patients using polymerase chain reaction and determined hTERT genotype by classifying the DNA band of 243 or 272 base pairs (bp) as S allele and 302 or 333 bp as long (L) allele. We compared overall survival using Kaplan-Meier estimates and equality of survival distributions using the log-rank test, and we computed univariate and multivariate Cox proportional hazards models to estimate the effects of selected variables.Overall survival differed significantly by hTERT MNS16A genotype, with median survivals of 25.1, 14.7, and 14.6 months for the SS, SL, and LL genotypes, respectively. Compared with the SS genotype, the hazard ratios for the SL and LL genotypes were 1.69 and 1.87, respectively, after adjustment for other factors. Multivariate Cox regression analysis showed an independent statistically significant association between the hTERT MNS16A variant genotype and outcome.A functional hTERT MNS16A genotype is a potential biomarker for assessment of survival outcome of GBM. Larger studies are needed to verify these findings.

    View details for DOI 10.1200/JCO.2005.04.0402

    View details for Web of Science ID 000236660200022

    View details for PubMedID 16575014

  • Risk factors of pancreatic cancer in the United States: Case-control study Hassan, M. M., Khan, R., Mestry, K., Bondy, M., Abbruzzese, J. L., Evans, D., Wolff, R. A., Chou, T., Ho, L., Xiong, H. H., Lenzi, R., Vauthey, J., Pisters, P. W., Li, D. AMER ASSOC CANCER RESEARCH. 2006
  • Antihistamine and anti-inflammatory drug use associated differently for high-grade versus low-grade gliomas Scheurer, M. E., Wrensch, M., El-Zein, R. A., Moghadassi, M., Miike, R., Aldape, K. D., Bondy, M. L. AMER ASSOC CANCER RESEARCH. 2006
  • Differing molecular pathology of pancreatic adenocarcinoma in Egyptian and United States patients. Soliman, A. S., Bondy, M., Webb, C., Schottenfeld, D. A., El-Ghawalby, N., Greenson, J., Abbruzzese, J. L., Hamilton, S. R. AMER ASSOC CANCER RESEARCH. 2006
  • Self-rated health among adult women of Mexican origin HISPANIC JOURNAL OF BEHAVIORAL SCIENCES Wilkinson, A. V., Hernandez-Valero, M. A., Etzel, C. J., Barcenas, C. H., Spitz, M. R., Bondy, M. L., Strom, S. S. 2006; 28 (1): 127–42

    Abstract

    Self-rated health (SRH), a consistent predictor of mortality among diverse populations, is sensitive to health indicators and social factors. American-born Hispanics report better SRH than their foreign-born counterparts but simultaneously report poorer health indicators and have shorter life expectancy. Using a matched prospective cross-sectional design, we analyzed data from 631 age-matched pairs of women, born in the United States or Mexico, enrolled in a cohort study based in Houston, Texas. Our first goal was to describe the relationships between SRH and health behaviors, physician-diagnosed chronic conditions, acculturation, and socioeconomic status (SES) by birthplace. Our second goal was to investigate the relative influence of SES, acculturation, health behaviors, and physician-diagnosed conditions in explaining expected differences in SRH between the two groups. Number of chronic conditions reported, particularly depression, more strongly influenced SRH than SES, acculturation, or reported health risk behaviors and the influence of birthplace is accounted for by these factors.

    View details for DOI 10.1177/0739986305283221

    View details for Web of Science ID 000234976900008

    View details for PubMedID 24600161

    View details for PubMedCentralID PMC3940416

  • Response to comments on 'Cytogenetic effects in children treated with methylphenidate' by El-Zein et al. CANCER LETTERS El-Zein, R. A., Hay, M. J., Lopez, M. S., Bondy, M. L., Morris, D. L., Legator, M. S., Abdel-Rahman, S. Z. 2006; 231 (1): 146–48

    View details for DOI 10.1016/j.canlet.2005.10.007

    View details for Web of Science ID 000234622600017

    View details for PubMedID 16290920

  • Polymorphisms of cytochrome P4501A2 and N-acetyltransferase genes, smoking, and risk of pancreatic cancer CARCINOGENESIS Li, D. H., Jiao, L., Li, Y. N., Doll, M. A., Hein, D. W., Bondy, M. L., Evans, D. B., Wolff, R. A., Lenzi, R., Pisters, P. W., Abbruzzese, J. L., Hassan, M. M. 2006; 27 (1): 103–11

    Abstract

    To test the hypothesis that genetic variation in the metabolism of tobacco carcinogens, such as aromatic amines (AA) and heterocyclic amines (HCA), contributes to pancreatic cancer, we have examined genetic polymorphisms of three key enzymes, i.e. cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 1 and 2 (NAT1 and NAT2), in a hospital-based case-control study of 365 patients with pancreatic adenocarcinoma and 379 frequency-matched healthy controls. Genotypes were determined using PCR-restriction fragment length polymorphism (RFLP) and Taqman methods. Smoking information was collected by personal interview. Adjusted odds ratio (AOR) and 95% confidence interval (CI) was estimated by unconditional multivariate logistic regression analysis. We found that the NAT1 'rapid' alleles were associated with a 1.5-fold increased risk of pancreatic cancer (95% CI: 1.0-2.1) with adjustment of potential confounders. This effect was more prominent among never smokers (AOR: 2.4, 95% CI: 1.4-4.3) and females (AOR: 1.8, 95% CI: 1.0-3.1). Some genotypes were significantly associated with increased risk for pancreatic cancer among smokers, especially heavy smokers (<20 pack years). For example, heavy smokers with the CYP1A2*1D (T-2467delT) delT, CYP1A2*1F(A-163C) C allele, NAT1 'rapid' or NAT2 'slow' alleles had an AOR (95% CI) of 1.4 (0.7-2.3), 1.9 (1.1-3.4), 3.0 (1.6-5.4) and 1.5 (0.8-2.6), respectively, compared with never smokers carrying the non-at-risk alleles. These effects were more prominent in females than in males. The corresponding AOR (95% CI) was 3.1 (1.0-8.0), 3.8 (1.5-10.1), 4.5 (1.6-12.7) and 2.0 (0.8-5.1) for females versus 1.0 (0.4-1.9), 1.1 (0.5-2.4), 2.1 (1.0-4.6) and 1.1 (0.5-2.6) for males. A significant synergistic effect of CYP1A2*1F C allele and NAT1"rapid" alleles on the risk for pancreatic cancer was also detected among never smokers (AOR: 2.9, 95% CI: 1.2-6.9) and among females (AOR: 2.5, 95% CI: 1.1-5.7). These data suggest that polymorphisms of the CYP1A2 and NAT1 genes modify the risk of pancreatic cancer.

    View details for DOI 10.1093/carcin/bgi171

    View details for Web of Science ID 000234219300010

    View details for PubMedID 15987714

    View details for PubMedCentralID PMC1350610

  • Modeling the impact of treatment and screening on U.S. breast cancer mortality: a Bayesian approach. Journal of the National Cancer Institute. Monographs Berry, D. A., Inoue, L., Shen, Y., Venier, J., Cohen, D., Bondy, M., Theriault, R., Munsell, M. F. 2006: 30–36

    Abstract

    BACKGROUND: Breast cancer mortality (BCM) in the United States declined from 33.1 per 100,000 women in 1990 to 26.6 per 100,000 women in 2000, yielding a 19.6% relative decline in BCM since 1990. Our goal is to apportion this decline between screening and therapy and to be able to state with some certainty that these interventions affected this decline.METHODS: We started with an age-appropriate population of 2,000,000 women in 1975 and monitored these women through 2000. On the basis of population data each year, we assigned screening and breast cancer to women. If a woman was diagnosed with breast cancer, we simulated a lifetime for her with death from breast cancer, and we modified this lifetime depending on the use of adjuvant therapy and whether the cancer was screen-detected. A woman's lifetime was taken as the minimum of her lifetime with death from breast cancer and her simulated natural lifetime. We used Bayesian simulation modeling, which allows for associating probability distributions with our estimates.RESULTS: We calculated the probabilities that screening mammography and adjuvant therapy contributed to the observed decline in BCM to be 90% and 99%, respectively. The posterior mean reduction in BCM due to screening is 10.6% +/- 5.7% and due to therapy is 19.5% +/- 5.4%. The decrease in the hazard of BCM due to tamoxifen use for ER-positive tumors is 37% +/- 14% and that due to adjuvant (nontaxane) chemotherapy is 15% +/- 14%.DISCUSSION: The spread in our posterior distributions reflect the uncertainty present in the data sources available to us. However, despite this uncertainty we conclude a high probability that both screening and improvements in therapy contributed to the reduction in BCM observed in the United States from 1990 to 2000.

    View details for PubMedID 17032892

  • A road map for efficient and reliable human genome epidemiology NATURE GENETICS Ioannidis, J. P., Gwinn, M., Little, J., Higgins, J. P., Bernstein, J. L., Boffetta, P., Bondy, M., Bray, M. S., Brenchley, P. E., Buffler, P. A., Casas, J. P., Chokkalingam, A., Danesh, J., Smith, G. D., Dolan, S., DUNCAN, R., Gruis, N. A., Hartge, P., Hashibe, M., Hunter, D. J., Jarvelin, M. R., Malmer, B., Maraganore, D. M., Newton-Bishop, J. A., O'Brien, T. R., Petersen, G., Riboli, E., Salanti, G., Seminara, D., Smeeth, L., Taioli, E., Timpson, N., Uitterlinden, A. G., Vineis, P., Wareham, N., Winn, D. M., Zimmern, R., Khoury, M. J. 2006; 38 (1): 3-5

    Abstract

    Networks of investigators have begun sharing best practices, tools and methods for analysis of associations between genetic variation and common diseases. A Network of Investigator Networks has been set up to drive the process, sponsored by the Human Genome Epidemiology Network. A workshop is planned to develop consensus guidelines for reporting results of genetic association studies. Published literature databases will be integrated, and unpublished data, including 'negative' studies, will be captured by online journals and through investigator networks. Systematic reviews will be expanded to include more meta-analyses of individual-level data and prospective meta-analyses. Field synopses will offer regularly updated overviews.

    View details for DOI 10.1038/ng0106-3

    View details for Web of Science ID 000234227200002

    View details for PubMedID 16468121

  • Selected polymorphisms of DNA repair genes and risk of pancreatic cancer CANCER DETECTION AND PREVENTION Jiao, L., Bondy, M. L., Hassan, M. M., Wolff, R. A., Evans, D. B., Abbruzzese, J. L., Li, D. 2006; 30 (3): 284–91

    Abstract

    Genetic variants of DNA repair genes may contribute to pancreatic carcinogenesis. O(6)-methylguanine-DNA methyltransferase (MGMT) is the major protein that removes alkylating DNA adducts, and apurinic/apyrimidinic endonuclease 1 (APE1) and X-ray repair cross-complementing group 1 (XRCC1) play important roles in the base excision repair pathway.We investigated the association between polymorphisms of MGMT (Leu(84)Phe and Ile(143)Val), APE1 (Asp(148)Glu), and XRCC1 (Arg(194)Trp and Arg(399)Gln) and risk of pancreatic cancer in a case-control study. Exposure information from 384 patients with primary pancreatic ductal adenocarcinoma and 357 cancer-free healthy controls were collected and genomic DNAs were genotyped for five markers. Controls were frequency matched to patients by age at enrollment (+/-5 years), gender, and race. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by using unconditional logistic regression models.There was no significant main effect or interaction with smoking of these genetic variants on the risk of pancreatic cancer. However, the XRCC1(194) polymorphism had a significant interaction with the APE1(148) (p=0.005) or MGMT(84) polymorphism (p=0.02) in modifying the risk of pancreatic cancer.This study suggests that polymorphisms of genes involved in the repair of alkylating DNA adduct and DNA base damage may play a role in modulating the risk of pancreatic cancer. Larger studies are required to validate these preliminary findings. The mechanism of the combined genotype effects remains to be elucidated.

    View details for DOI 10.1016/j.cdp.2006.05.002

    View details for Web of Science ID 000240393300010

    View details for PubMedID 16844323

    View details for PubMedCentralID PMC1857309

  • Cytogenetic effects in children treated with methylphenidate CANCER LETTERS El-Zein, R. A., Abdel-Rahman, S. Z., Hay, M. J., Lopez, M. S., Bondy, M. L., Morris, D. L., Legator, M. S. 2005; 230 (2): 284–91

    Abstract

    In recent years there has been a surge in methylphenidate (Ritalin) use for treatment of attention deficit/hyperactivity disorder (ADHD) in children. However, there is a paucity of information on whether this drug poses any potential health risks, such as mutagenicity or carcinogenicity, for humans. To address this issue, we investigated whether this central nervous system stimulant produces cytogenetic abnormalities in pediatric patients at therapeutic levels. In a population composed of twelve children treated with therapeutic doses of methylphenidate, we analyzed three cytogenetic endpoints in peripheral blood lymphocytes obtained before and three months after initiation of treatment with this drug. In all participants, treatment induced a significant 3, 4.3 and 2.4-fold increase in chromosome aberrations, sister chromatid exchanges and micronuclei frequencies, respectively (P=0.000 in all cases). These findings warrant further investigations of the possible health effects of methylphenidate in humans, especially in view of the well-documented relationship between elevated frequencies of chromosome aberrations and increased cancer risk.

    View details for DOI 10.1016/j.canlet.2005.01.003

    View details for Web of Science ID 000233794600011

    View details for PubMedID 16297714

  • Differing DNA methylation patterns and gene mutation frequencies in colorectal carcinomas from Middle Eastern countries CLINICAL CANCER RESEARCH Chan, A. O., Soliman, A. S., Zhang, Q., Rashid, A., Bedeir, A., Houlihan, P. S., Mokhtar, N., Al-Masri, N., Ozbek, U., Yaghan, R., Kandilci, A., Omar, S., Kapran, Y., Dizdaroglu, F., Bondy, M. L., Amos, C. I., Issa, J. P., Levin, B., Hamilton 2005; 11 (23): 8281–87

    Abstract

    The epidemiology of colorectal carcinoma is well known to differ among countries but the molecular characteristics are usually assumed to be similar. International differences in molecular pathology have not been studied extensively but have implications for the management of patients in different countries and of immigrant patients.We evaluated the CpG island methylator phenotype pathway characterized by concordant methylation of gene promoters that often silences transcription of the genes, the microsatellite instability pathway, and K-ras and p53 gene status in 247 colorectal carcinomas from the three selected Middle Eastern countries of Egypt, Jordan, and Turkey.Colorectal carcinoma from Egypt had the lowest frequencies of methylation. In multinomial logistic regression analysis, Jordanian colorectal carcinoma more frequently had methylation involving the p16 tumor suppressor gene (odds ratio, 3.5; 95% confidence interval, 1.2-10.6; P = 0.023) and MINT31 locus (odds ratio, 2.3; 95% confidence interval, 1.0-5.1; P = 0.041). The K-ras proto-oncogene was more frequently mutated in colorectal carcinoma from Turkey (odds ratio, 2.9; 95% confidence interval, 1.2-6.7; P = 0.016), but p53 overexpression was more common in both Jordanian and Turkish colorectal carcinoma than in Egyptian cases (odds ratio, 2.5; 95% confidence interval, 1.2-5.5; P = 0.019; and odds ratio, 3.6; 95% confidence interval, 1.8-7.1; P = 0.0003, respectively). The findings in Turkish colorectal carcinoma were most similar to those reported for Western cases.Colorectal carcinoma from Middle Eastern countries have differing gene methylation patterns and mutation frequencies that indicate dissimilar molecular pathogenesis, probably reflecting different environmental exposures. These molecular differences could affect prevention strategies, therapeutic efficacy, and transferability of clinical trial results.

    View details for DOI 10.1158/1078-0432.CCR-05-1000

    View details for Web of Science ID 000233701300010

    View details for PubMedID 16322286

  • Epidemiology of intracranial meningioma NEUROSURGERY Claus, E. B., Bondy, M. L., Schildkraut, J. M., Wiemels, J. L., Wrensch, M., Black, P. M. 2005; 57 (6): 1088–94

    Abstract

    Meningiomas are the most frequently reported primary intracranial neoplasms, accounting for approximately 25% of all such lesions diagnosed in the United States. Few studies have examined the risk factors associated with a diagnosis of meningioma with two categories of exposure, hormones (both endogenous and exogenous) and radiation, most strongly associated with meningioma risk. Limited data are also available on long-term outcomes for meningioma patients, although it is clear that the disease is associated with significant morbidity and mortality. Recent legislation passed in the United States (The Benign Brain Tumor Cancer Registries Amendment Act [H.R. 5204]) mandates registration of benign brain tumors such as meningioma. This will increase the focus on this disease over the coming years as well as likely increase the reported prevalence of the disease. The increased emphasis on research dedicated to the study of brain tumors coupled with the advent of new tools in genetic and molecular epidemiology make the current era an ideal time to advance knowledge for intracranial meningioma. This review highlights current knowledge of meningioma epidemiology and new directions for research efforts in this field.

    View details for DOI 10.1227/01.NEU.0000188281.91351.B9

    View details for Web of Science ID 000233826300014

    View details for PubMedID 16331155

  • Human telomerase genetic variation predicts survival of patients with glioblastoma multiforme Wang, L., El-Zein, R., Aldape, K., Gilbert, M., Wei, Q., Bondy, M. DUKE UNIV PRESS. 2005: 288
  • Methylation and messenger RNA expression of p15(INK4b) but not p16(INK4a) are independent risk factors for ovarian cancer CLINICAL CANCER RESEARCH Liu, Z. S., Wang, L. E., Wang, L., Lu, K. H., Mills, G. B., Bondy, M. L., Wei, Q. Y. 2005; 11 (13): 4968–76

    Abstract

    The purpose of this research was to compare methylation status and mRNA expression of p15INK4b and p16INK4a in serous epithelial ovarian cancer tissues and normal ovarian tissues.We analyzed the DNA methylation status and mRNA expression of p15INK4b and p16INK4a in 52 ovarian cancer specimens and 40 normal ovarian specimens by using methylation-specific PCR and real-time reverse transcription-PCR, respectively.Although the p15INK4b and p16INK4a mRNA expression levels were highly correlated with each other (P < 0.001), the methylation status did not seem to be linked with levels of mRNA expression, as no association between the two events was found for either gene. Promoter hypermethylation of p15(INK4b) was more common in ovarian cancer (30.8% for the 52 cases) than in normal ovaries (5% for the 40 controls without ovarian cancer; P = 0.005) but not methylation of p16INK4a (25% for cancer versus 37.5% for normal; P = 0.288). The relative mRNA expression levels of p15INK4b were significantly lower in ovarian cancer (12.9%) than in normal ovaries (41.7%; P = 0.008) but not those of p16INK4a (27% for cases versus 32.8% for controls; P = 0.754). Only high methylation rate and low mRNA expression of p15INK4b were independent risk factors for ovarian cancer (adjusted odds ratio, 5.67; 95% confidence interval, 0.85-37.9 for high methylation rate and odds ratio, 8.98; 95% confidence interval, 1.58-50.9 for low mRNA expression, respectively).Our results suggest that epigenetic alterations in p15INK4b but not p16INK4a have an important role in ovarian carcinogenesis and that mechanisms other than methylation may exist to reduce gene expression of p15INK4b in ovarian cancer.

    View details for DOI 10.1158/1078-0432.CCR-04-2293

    View details for Web of Science ID 000230400300045

    View details for PubMedID 16000597

  • Effects of nativity, age at migration, and acculturation on smoking among adult Houston residents of Mexican descent AMERICAN JOURNAL OF PUBLIC HEALTH Wilkinson, A. V., Spitz, M. R., Strom, S. S., Prokhorov, A. V., Barcenas, C. H., Cao, Y. M., Saunders, K. C., Bondy, M. L. 2005; 95 (6): 1043–49

    Abstract

    We investigated differences in smoking behaviors between US-and Mexican-born ever smokers and examined the influence of US culture on smoking initiation.Participants were 5030 adults of Mexican descent enrolled in an ongoing population-based cohort in Houston, Tex.More men than women reported current smoking; rates among US-born women were higher than those among Mexican-born women. Smoking rates among US-born men were higher than earlier published rates among Hispanics and non-Hispanic Whites but similar to rates among African Americans. Current smoking rates among Mexican-born women were lower than published rates for Hispanics, non-Hispanic Whites, and African Americans. Older age, male gender, a higher level of acculturation, more than a high school education, and residing in a census tract with a higher median age predicted history of smoking among US-born participants. Among Mexican-born participants, older age, male gender, a higher level of acculturation, and younger age at migration predicted history of smoking.Smoking interventions for people of Mexican descent should be tailored according to gender, nativity, and acculturation level and should target all ages, not just young people.

    View details for DOI 10.2105/AJPH.2004.055319

    View details for Web of Science ID 000229381800031

    View details for PubMedID 15914831

    View details for PubMedCentralID PMC1449306

  • 5,10-Methylenetetrahydrofolate reductase polymorphisms and the risk of pancreatic cancer CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Li, D. H., Ahmed, M., Li, Y. N., Jiao, L., Chou, T. H., Wolff, R. A., Lenzi, R., Evans, D. B., Bondy, M. L., Pisters, P. W., Abbruzzese, J. L., Hassan, M. M. 2005; 14 (6): 1470–76

    Abstract

    To test the hypothesis that 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms modify the risk of pancreatic cancer, we conducted a hospital-based, case-control study involving 347 patients with newly diagnosed pancreatic adenocarcinoma and 348 healthy controls, frequency matched by age, sex, and race. MTHFR polymorphisms were determined using the PCR-RFLP method. Association of these polymorphisms with the risk of pancreatic cancer was estimated by unconditional logistic regression analysis. We found that the C667T (but not the A1298C) polymorphism had a significant main effect on the risk of pancreatic cancer. The frequencies of the MTHFR 667CC, 667CT, and 667TT genotypes were 49.5%, 38.6%, and 11.9%, respectively, among cases compared with 48.5%, 45.0%, and 6.5%, respectively, among controls. Individuals with the 667TT genotype displayed a 2-fold increased risk for pancreatic cancer compared with those with the CC/CT genotypes [adjusted odds ratio (OR), 2.14; 95% confidence interval (95% CI), 1.14-4.01]. Multivariate analyses found that the effect of the 677TT genotype on the risk of pancreatic cancer was present among ever smokers (OR, 5.53; 95% CI, 2.0-15.3) and ever alcohol drinkers (OR, 3.16; 95% CI, 1.30-7.69) but not in never smokers (OR, 0.82; 95% CI, 0.33-2.06) and never drinkers (OR, 1.42; 95% CI, 0.56-3.62). Furthermore, a positive interaction between the MTHFR TT genotype and heavy smoking or heavy alcohol consumption was detected. The OR (95% CI) of pancreatic cancer was 6.83 (1.91-24.38) for heavy smokers among the TT carriers compared with never smokers with the CC/CT genotypes and 4.23 (0.88-20.3) for heavy drinkers with the TT genotype compared with nondrinkers with the CC/CT genotypes. These observations support a role for folate metabolism in pancreatic cancer, especially among smokers and heavy drinkers.

    View details for DOI 10.1158/1055-9965.EPI-04-0894

    View details for Web of Science ID 000229766600024

    View details for PubMedID 15941958

  • Breast cancer treatment guidelines in older women JOURNAL OF CLINICAL ONCOLOGY Giordano, S. H., Hortobagyi, G. N., Kau, S. W., Theriault, R. L., Bondy, M. L. 2005; 23 (4): 783–91

    Abstract

    To determine patterns and predictors of concordance with institutional treatment guidelines among older women with breast cancer.The study population included 1,568 patients aged 55 years and older who were treated at M.D. Anderson Cancer Center between July 1997 and January 2002 for stage I to IIIA invasive ductal and lobular breast cancer. Concordance with institutional guidelines was determined for definitive surgical therapy, radiotherapy after breast-conserving surgery, radiation therapy after mastectomy, adjuvant chemotherapy use, and adjuvant hormonal therapy use. The following variables were considered as possible modifiers of concordance: patient age, marital status, race, educational level, Eastern Cooperative Oncology Group performance status, comorbidity score, clinical stage, hormone receptor status, HER2-neu status, tumor grade, pathologic tumor size, lymphatic invasion, and number of lymph nodes involved. Logistic regression modeling was performed to determine the independent effect of each variable on guideline concordance.Older women were less likely to receive treatment in concordance with guidelines for definitive surgical therapy (P < .001), postlumpectomy radiation (P = .03), adjuvant chemotherapy (P < .001), and adjuvant hormonal therapy (P < .001). In multivariate analysis, age > or = 75 years predicted a deviation from guidelines for definitive surgical therapy, adjuvant chemotherapy, and adjuvant hormonal therapy. Nonwhite race was associated with decreased likelihood of adjuvant radiation therapy after breast conservation.After adjustment for comorbidity score, race, marital status, educational status, clinical stage, and tumor characteristics, increasing patient age was independently associated with decreased guideline concordance for definitive surgery, adjuvant chemotherapy, and adjuvant hormonal therapy. Future research should focus on delineating the possible reasons for guideline discordance.

    View details for DOI 10.1200/JCO.2005.04.175

    View details for Web of Science ID 000226738900018

    View details for PubMedID 15681522

  • A pilot case-control study of gamma-radiation sensitivity and risk of papillary thyroid cancer THYROID Xiong, P., Zheng, R., Wang, L. E., Bondy, M. L., Shen, H. B., Borer, M. M., Wei, Q. Y., Sturgis, E. M. 2005; 15 (2): 94–99

    Abstract

    In vitro gamma-radiation-induced chromatid breaks per cell (b/c) in lymphocytes may be associated with risk of papillary thyroid cancer (PTC). This pilot case-control study involved 106 patients with thyroid disease (57 with PTC and 49 with benign thyroid disease) and 105 cancer-free matched controls. Multivariate logistic regression analyses identified that an elevated gamma-radiation-induced b/c value was a risk factor for PTC (adjusted odds ratio = 4.54; 95% CI, 2.07-9.95), and a dose-response relationship was evident when the b/c values were categorized into tertiles. High levels of chromatid breaks induced by gamma-radiation may constitute an independent risk factor for PTC, but further study is needed.

    View details for DOI 10.1089/thy.2005.15.94

    View details for Web of Science ID 000227544500002

    View details for PubMedID 15753665

  • Clinicopathologic characteristics and prognostic factors in 420 metastatic breast cancer patients with central nervous system metastases. Altundag, K., Bondy, M. L., Kau, S. W., Broglio, K., Rivera, E. SPRINGER. 2005: S143
  • Effect of dietary intake of phytoestrogens on estrogen receptor status in premenopausal women with breast cancer NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL Touillaud, M. S., Pillow, P. C., Jakovljevic, J., Bondy, M. L., Singletary, S. E., Li, D. H., Chang, S. N. 2005; 51 (2): 162–69

    Abstract

    Although many dietary studies have focused on breast cancer risk, few have examined dietary influence on tumor characteristics such as estrogen receptor (ER) status. Because phytoestrogens may modulate hormone levels and ER expression, we analyzed ER status and phytoestrogen intake in a case-case study of 124 premenopausal breast cancer patients. We assessed intake with a food-frequency questionnaire and obtained ER status from medical records. Rather than focusing on risk, we evaluated whether low intakes were more strongly associated with ER-negative tumors than with ER-positive disease. In logistic regression adjusting for potential confounders, threefold greater risks of ER-negative tumors relative to ER-positive tumors were associated with low intake of the isoflavones genistein (odds ratio, OR=3.50; 95% confidence interval, CI=1.43-8.58) and daidzein (OR=3.10; 95% CI=1.31-7.30). Low intake of the flavonoid kaempferol (OR=0.36; 95% CI=0.16-0.83), the trace element boron (OR=0.33; 95% CI=0.13-0.83), and the phytosterol beta-sitosterol (OR=0.42; 95% CI=0.18-0.98) were associated with decreased risk of ER-negative tumors relative to ER-positive disease. Other phytoestrogens were not significantly associated with ER status. Thus, in premenopausal patients, some phytoestrogens may affect breast carcinogenesis by influencing ER status. Such findings suggest new directions for mechanistic research on dietary factors in breast carcinogenesis that may have relevance for prevention and clinical treatment.

    View details for DOI 10.1207/s15327914nc5102_6

    View details for Web of Science ID 000229157500006

    View details for PubMedID 15860438

  • Adult glioma incidence trends in the United States, 1977-2000 CANCER Hess, K. R., Broglio, K. R., Bondy, M. L. 2004; 101 (10): 2293–99

    Abstract

    Several authors have reported an increase in the incidence of brain tumors, especially among the elderly. A more complete understanding of adult glioma incidence trends might provide indications of risk factors for gliomas and contribute to the search for improved therapies.The authors used the Surveillance, Epidemiology, and End Results (SEER) registry public use data tapes, which included data on patients with cancer diagnosed between 1973 and 2000. For 3 histologies as well as for 12 histology categories combined, the authors used Poisson regression to model incidence as a function of year of diagnosis, age at diagnosis, race (white or African American), and gender. They used cubic splines to fit age at diagnosis and year of diagnosis and tested for all pair-wise interactions.The interaction between year of diagnosis and age at diagnosis was significant in all four groups modeled. In glioblastoma, there was also a significant interaction between gender and age at diagnosis. In anaplastic astrocytoma, there was a significant interaction between gender and year of diagnosis. In oligodendroglioma, there was a significant interaction between race and gender. In the 12 histology categories combined, there was a significant interaction between gender and age at diagnosis.The results in the current study were consistent with other published reports that showed an increase in the incidence of brain tumors using SEER data. Although others have observed increasing incidence trends among the elderly, the authors formally tested and found a statistically significant interaction between age at diagnosis and year of diagnosis.

    View details for DOI 10.1002/cncr.20621

    View details for Web of Science ID 000225081300021

    View details for PubMedID 15476282

  • Glutathione S-transferase (GST) polymorphisms and outcomes in central nervous system (CNS) tumors in childhood and adolescents Okcu, M. F., Shu, Q., Li, X. N., Dinu, B., Perlaky, L., Bondy, M., Armstrong, D. L., Adekunle, A., Bhattacharjee, M. B., Dauser, R. C., Chintagumpala, M., Blaney, S., Lau, C. DUKE UNIV PRESS. 2004: 412
  • Reduced DNA repair of benzo[a]pyrene diol epoxide-induced adducts and common XPD polymorphisms in breast cancer patients CARCINOGENESIS Shi, Q. L., Wang, L. E., Bondy, M. L., Brewster, A., Singletary, S. E., Wei, Q. Y. 2004; 25 (9): 1695–1700

    Abstract

    Environmental chemicals are thought to play a role in the etiology of breast cancer, because polycyclic acromatic hydrocarbon (PAH)-DNA adducts are detectable in normal and malignant breast tissues. Peripheral blood lymphocytes (PBLs) from female breast cancer patients were more sensitive to in vitro exposure to benzo[a]pyrene diol epoxide (BPDE) than those from healthy controls. Therefore, we hypothesized that reduced DNA repair is associated with risk of breast cancer in women and the risk may be modulated by polymorphisms of DNA repair genes. In a case-control pilot study, we included 69 previously untreated female breast cancer patients and 79 controls frequency matched to the cases on age and ethnicity. The PBLs were used to measure DNA repair capacity (DRC) by using the host-cell reactivation (HCR) assay with a reporter gene damaged by exposure to 60 micro M BPDE prior to transfection. We also genotyped for two common XPD polymorphisms Lys751Gln and Asp312Asn. We found that the mean DRC level was significantly lower in breast cancer patients (10.1%) than in controls (11.1%) (P = 0.008). Subjects with DRC lower than the median level of controls (11.0%) had >3-fold increased risk (OR = 3.36, 95% CI = 1.15-9.80) for breast cancer than did those with higher DRC after adjustment for age, smoking status and assay-related variables. None of the genotypes was statistically significantly associated with an increased risk of breast cancer, which may be due to the small number of observations in each subgroup. The XPD variant genotypes in general predicted the DRC better in the controls than in the cases, suggesting genetic variants of other DNA repair genes may be involved in these breast cancer patients. These findings suggest that women with reduced DRC may be at an increased risk of developing breast cancer. Large studies are warranted to confirm these preliminary findings.

    View details for DOI 10.1093/carcin/bgh167

    View details for Web of Science ID 000223588800017

    View details for PubMedID 15090466

  • Polymorphisms of DNA repair genes and risk of glioma CANCER RESEARCH Wang, L. E., Bondy, M. L., Shen, H. B., El-Zein, R., Aldape, K., Cao, Y. M., Pudavalli, Levin, V. A., Yung, W. K., Wei, Q. Y. 2004; 64 (16): 5560–63

    Abstract

    DNA repair genes play a major role in maintaining genomic stability through different repair pathways that are mediated by cell cycle control genes such as p53. We found previously that glioma patients were susceptible to gamma-ray-induced chromosomal breaks, which may be influenced by genetic variation in genes involved in DNA strand breaks, such as XRCC1 in single-strand break repair, XRCC3 and RAD51 in homologous recombination repair, and XRCC7 in nonhomologous end joining double-strand break repair. Therefore, we tested the hypothesis that genetic polymorphisms in XRCC1, XRCC3, RAD51, XRCC7, and p53 were associated with risk of glioma in 309 patients with newly diagnosed glioma and 342 cancer-free control participants frequency matched on age (+/- 5 years), sex, and self-reported ethnicity. We did not find any statistically significant differences in the distributions of XRCC1 Arg399Gln, XRCC3 Thr241Met, RAD51 G135C, and P53 Arg72Pro polymorphisms between the cases and the controls. However, the XRCC7 G6721T variant T allele and TT genotype were more common in the cases (0.668 and 43.4%, respectively) than in the controls (0.613 and 38.9%, respectively), and the differences were statistically significant (P = 0.045 and 0.040, respectively). The adjusted odds ratios were 1.78 (95% confidence interval, 1.08-2.94) and 1.86 (95% confidence interval, 1.12-3.09) for the GT heterozygotes and TT homozygotes, respectively. The combined T variant genotype (GT+TT) was associated with a 1.82-fold increased risk of glioma (95% confidence interval, 1.13-2.93). These results suggest that the T allele may be a risk allele, and this XRCC7 polymorphism may be a marker for the susceptibility to glioma. Larger studies are needed to confirm our findings and unravel the underlying mechanisms.

    View details for DOI 10.1158/0008-5472.CAN-03-2181

    View details for Web of Science ID 000223321900007

    View details for PubMedID 15313891

  • Day care, childhood infections, and risk of neuroblastoma AMERICAN JOURNAL OF EPIDEMIOLOGY Menegaux, F., Olshan, A. F., Neglia, J. P., Pollock, B. H., Bondy, M. L. 2004; 159 (9): 843–51

    Abstract

    Neuroblastoma is the most common cancer in infants worldwide, but little is known about its etiology. Infectious etiologies involving the immune system have been hypothesized for some childhood cancers, especially leukemia, but the role of infectious agents in neuroblastoma has not been fully investigated. The authors used data from a large case-control study conducted by the Children's Oncology Group in the United States and Canada in 1992-1994 to investigate whether there was any relation among day-care attendance, childhood infections, allergies, and neuroblastoma. They interviewed mothers of 538 case children and 504 age-matched control children by telephone about several factors, including pregnancy, medical history, lifestyle, and childhood medical conditions and exposures. The results suggested decreased risks associated with day-care attendance (odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.56, 1.17), childhood infectious diseases (chickenpox, mumps, red measles, and German measles) (OR = 0.60, 95% CI: 0.39, 0.93), and allergies (OR = 0.68, 95% CI: 0.44, 1.07). The authors found reduced neuroblastoma risk associated with markers of potential childhood infections. This suggests a possible role of infectious agents in neuroblastoma etiology. Future epidemiologic studies should incorporate more direct data on infection.

    View details for DOI 10.1093/aje/kwh111

    View details for Web of Science ID 000221299800004

    View details for PubMedID 15105177

    View details for PubMedCentralID PMC2080646

  • Glutathione S-transferase polymorphisms and survival in primary malignant glioma CLINICAL CANCER RESEARCH Okcu, M. F., Selvan, M., Wang, L. E., Stout, L., Erana, R., Airewele, G., Adatto, P., Hess, K., Ali-Osman, F., Groves, M., Yung, A. W., Levin, V. A., Wei, Q. Y., Bondy, M. 2004; 10 (8): 2618–25

    Abstract

    The purpose of this research was to investigate the relationship between glutathione S-transferase (GST) polymorphisms and survival, and chemotherapy-related toxicity in 278 glioma patients.We determined genetic variants for GSTM1, GSTT1, and GSTP1 enzymes by PCR and restriction fragment length polymorphisms. We conducted Kaplan-Meier and Cox-proportional hazard analyses to examine whether the GST polymorphisms are related to overall survival, and logistic regression analysis to explore whether the GST polymorphisms are associated with toxicity.For patients with anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, and anaplastic ependymoma (n = 78), patients with GSTP1*A/*A-M1 null genotype survived longer than did the rest of the group (median survival "not achieved," and 41 months, respectively; P = 0.06). Among patients treated with nitrosoureas (n = 108), those with GSTP1*A/*A and GSTM1 null genotype were 5.7 times (95% confidence interval, 0.9-37.4) more likely to experience an adverse event secondary to chemotherapy, compared with the others.In patients with anaplastic astrocytoma, anaplastic oligodendroglioma, and anaplastic oligoastrocytoma, combination of germ-line GSTP1*A/*A and GSTM1 null genotype confers a survival advantage. Patients with this genotype also have an increased risk of adverse events secondary to chemotherapy that primarily comprised nitrosourea alkylating agents.

    View details for DOI 10.1158/1078-0432.CCR-03-0053

    View details for Web of Science ID 000220933800007

    View details for PubMedID 15102663

  • Maternal medication use and neuroblastoma in offspring AMERICAN JOURNAL OF EPIDEMIOLOGY Cook, M. N., Olshan, A. F., Guess, H. A., Savitz, D. A., Poole, C., Blatt, J., Bondy, M. L., Pollock, B. H. 2004; 159 (8): 721–31

    Abstract

    The association between a mother's use of specific medications during pregnancy and lactation and neuroblastoma in her offspring was evaluated in a case-control study. Newly diagnosed cases of neuroblastoma (n=504) in the United States and Canada were identified between 1992 and 1994 at 139 hospitals affiliated with the Pediatric Oncology Group or the Children's Cancer Group clinical trial programs. One age-matched control was sampled from the community of each case by means of random digit dialing. Exposure information was ascertained retrospectively from mothers in a structured telephone interview. Odds ratios were estimated using conditional logistic regression, with adjustment for maternal sociodemographic factors. The results did not support an association between neuroblastoma and maternal exposure to diuretic agents, antiinfective agents, estrogens, progestins, sedatives, anticonvulsant drugs, or drugs that may form N-nitroso derivatives. Mothers of cases were more likely to report using medications containing opioid agonists while they were pregnant or nursing than were mothers of controls (odds ratio=2.4, 95% confidence interval: 1.3, 4.3). Specifically, more mothers of cases reported using medications containing codeine while pregnant or nursing than did mothers of controls (odds ratio=3.4, 95% confidence interval: 1.4, 8.4). This preliminary finding may be due to bias, confounding, or chance, and additional studies are needed for confirmation.

    View details for DOI 10.1093/aje/kwh108

    View details for Web of Science ID 000220613600001

    View details for PubMedID 15051581

  • Racial differences in diagnosis, treatment, and clinical delays in a population-based study of patients with newly diagnosed breast carcinoma CANCER Gwyn, K., Bondy, M. L., Cohen, D. S., Lund, M. J., Liff, J. M., Flagg, E. W., Brinton, L. A., Eley, J. W., Coates, R. J. 2004; 100 (8): 1595–1604

    Abstract

    Few studies have addressed the issue of whether delays in the interval between medical consultation and the diagnosis and treatment of breast carcinoma are greater for African American women than for white women. The authors examined differences with respect to these delays and analyzed the factors that may have contributed to such differences among women ages 20-54 years who had invasive breast carcinoma diagnosed between 1990 and 1992 and who lived in Atlanta, Georgia.A total of 251 African American women and 580 white women were interviewed and had their medical records reviewed. The authors estimated racial differences in delay times and used polytomous logistic regression to determine the contributions of various factors (socioeconomic and other) to these differences.Although most women in both groups were treated within 3 months of initial consultation, 22.4% of African American women and 14.3% of white women had clinical delays of > 3 months. Compared with white women, African American women were more likely to experience delays in diagnosis and treatment. Access to care (as represented by method of detection and insurance status) and poverty index partially accounted for these differences in delay time; however, racial differences in terms of delayed treatment and diagnosis remained even after adjustment for contributing factors.The findings of the current study suggest that among women ages 20-54 years who have breast carcinoma, potentially clinically significant differences in terms of delayed diagnosis and treatment exist between African American women and white women. Improvements in access to care and in socioeconomic circumstances may address these differences to some degree, but additional research is needed to identify other contributing factors.

    View details for DOI 10.1002/cncr.20169

    View details for Web of Science ID 000220725400006

    View details for PubMedID 15073845

  • A Ser49Cys variant in the ataxia telangiectasia, mutated, gene that is more common in patients with breast carcinoma compared with population controls CANCER Buchholz, T. A., Weil, M. M., Ashorn, C. L., Strom, E. A., Sigurdson, A., Bondy, M., Chakraborty, R., Cox, J. D., McNeese, M. D., Story, M. D. 2004; 100 (7): 1345–51

    Abstract

    Mothers of children who have ataxia telangiectasia have been reported to be at increased risk for development of breast carcinoma. To test whether sequence variants in the ataxia telangiectasia, mutated, gene (ATM) are associated with breast carcinoma, the authors compared the frequency of ATM cDNA sequence changes in patients with breast carcinoma with the corresponding frequency in control patients.The authors sequenced ATM cDNA from 91 patients with breast carcinoma and compared the frequencies of sequence changes in these patients with the corresponding frequencies in a control sample of 940 individuals with no history of malignant disease.Thirty-five patients with breast carcinoma had one or more single-base changes in ATM. Three genetic variants were found in at least two patients. These variants resulted in Asp1853Asn, Pro1054Arg, or Ser49Cys amino acid substitutions in the ATM protein. The Ser49Cys variant was more common in patients with breast carcinoma than in the control patients, with respective frequencies of 6.7% (5 of 75 patients) and 1.3% (12 of 940 patients; P=0.006; Fisher two-sided exact test). The subgroup of patients with bilateral breast carcinoma had a Ser49Cys frequency of 11.8% (2 of 17 patients), which again was significantly different from what was observed in the control group (P=0.024; Fisher two-sided exact test). The allele frequencies of the other two variants were not different between case patients and control patients.Patients with breast carcinoma, particularly those with bilateral disease, were more likely to have a variant in the ATM gene that resulted in a Ser49Cys substitution in the gene product. Additional studies are needed to evaluate the potential functional consequences of the Ser49Cys substitution and confirm the relevance of this variant in the development of breast carcinoma.

    View details for DOI 10.1002/cncr.20133

    View details for Web of Science ID 000220341000004

    View details for PubMedID 15042666

  • High levels of oxidative DNA damage in lymphocyte DNA of premenopausal breast cancer patients from Egypt INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH Soliman, A. S., Vulimiri, S. V., Kleiner, H. E., Shen, J. J., Eissa, S., Morad, M., Taha, H., Lukmanji, F., Li, D. H., Johnston, D. A., Lo, H. H., Lau, S., Digiovanni, J., Bondy, M. L. 2004; 14 (2): 121–34

    Abstract

    Egypt shows a parallel increase in premenopausal breast cancer and environmental pollution. The purpose of this study is to explore a possible relationship between oxidative DNA damage, urinary estrogen metabolites and breast cancer in Egyptian premenopausal women. We conducted a pilot study of Egyptian breast cancer involving 29 cases and 32 controls and analysed lymphocyte DNA levels of 7,8-dihydro-8-oxo-2'-deoxyguanine (8-oxo-dG), a measure of oxidative DNA damage using high performance liquid chromatography with electro-chemical detection (HPLC-ECD) method. We analysed levels of urinary estrogen metabolites, 2-hydroxyestrone (2-OHE) and 16alpha-hydroxyestrone (16alpha-OHE) by an enzyme immuno assay. We also collected residential, occupational, and reproductive histories of all study subjects. We detected, in all subjects, exceptionally high levels of 8-oxo-dG and thus oxidative DNA damage, the levels (mean 8-oxo-dG/10(5) dG+/-SD) were significantly (P<0.01) higher in breast cancer cases (139.4+/-78.4) than in controls (60.9+/-51.5). Urinary 2-OHE and 16alpha-OHE or their ratio was not significantly different between cases and controls. However, 8-oxo-dG levels were positively correlated (P<0.05) with 2-OHE and 16alpha-OHE from cases while controls showed a negative correlation (P<0.05). Urban residence (Odds Ratio [OR] 3.1; Confidence interval [CI], 1.1-9.3), infertility (OR [9.8]; CI [1.1-89.7]), age (OR [2.6]; CI [1.4-4.6]) and 8-oxo-dG (OR 5.8; CI 1.9-17.5) levels were found to be significant predictors of breast cancer. Our finding of exceptionally high levels of 8-oxo-dG, a common result of oxidative DNA damage, warrant future studies on a larger population of premenopausal women in Egypt with consideration of other susceptibility markers and dietary characteristics.

    View details for DOI 10.1080/0960312042000209534

    View details for Web of Science ID 000220754900003

    View details for PubMedID 15203457

  • Estimated risk in malignancy: the emerging field of molecular epidemiology. Clinical advances in hematology & oncology : H&O Bondy, M. 2004; 2 (3): 147–51

    View details for PubMedID 16166941

  • Gamma radiation sensitivity and risk of malignant and benign salivary gland tumors - A pilot case-control analysis CANCER Zheng, R., Wang, L. E., Bondy, M. L., Wei, Q. Y., Sturgis, E. M. 2004; 100 (3): 561–67

    Abstract

    The salivary gland is a highly radiosensitive organ. Exposure to gamma radiation is a risk factor for both malignant (MSTs) and benign salivary gland tumors (BSTs), but the exact mechanisms remain unknown. The objectives of the current study were to determine whether gamma radiation-induced chromatid breaks increase the risk of MSTs and BSTs and whether there is any difference in risk between these two diseases.The authors performed a pilot case-control study of 57 patients with salivary gland diseases (45 patients with MSTs and 12 patients with BSTs) and 105 cancer-free controls. Peripheral blood lymphocytes from these participants were cultured and exposed to gamma radiation (1.5 grays). Five hours later, metaphase spread slides were evaluated. The chromatid breaks in 50 well-spread metaphase slides were counted to determine the average number of chromatid breaks per cell (b/c).Multivariate logistic regression analyses revealed that gamma radiation-induced b/c values greater than the median of the controls were a significant risk factor for salivary gland tumors (adjusted odds ratio [OR], 17.25; 95% confidence interval [CI], 4.92-60.49). The risk remained significant for MSTs (adjusted OR, 40.45; 95% CI, 5.27-310.17) but was of borderline significance for BSTs (adjusted OR, 4.73; 95% CI, 0.94-23.87) when these tumors were analyzed separately.In the current study, high levels of chromatid breaks in lymphocytes induced by gamma irradiation were associated with an independent risk for MSTs and were likely to increase the risk of BSTs. However, larger studies are needed to verify these findings.

    View details for DOI 10.1002/cncr.11944

    View details for Web of Science ID 000188611400016

    View details for PubMedID 14745873

  • Effects of smoking and radiotherapy on lung carcinoma in breast carcinoma survivors CANCER Ford, M. B., Sigurdson, A. J., Petrulis, E. S., Ng, C. S., Kemp, B., Cooksley, C., McNeese, M., Selwyn, B. J., Spitz, M. R., Bondy, M. L. 2003; 98 (7): 1457–64

    Abstract

    The combined effects of thoracic radiotherapy (XRT) and cigarette smoking are not known with certainty, but they have important implications for lung carcinogenesis after cancer therapy in some patients. The authors analyzed smoking, radiation, and both exposures on lung carcinoma development in women who were treated previously for breast carcinoma.Case patients (n = 280) were female residents of the United States, ages 30-89 years, with breast carcinoma prior to primary lung carcinoma diagnosed between 1960 and 1997. Control patients (n = 300) were selected randomly from 37,000 patients with breast carcinoma who were treated at The University of Texas M. D. Anderson Cancer Center and frequency matched with women in the case group based on age at diagnosis (5-year strata), ethnicity, year of breast carcinoma diagnosis (5-year strata), and survival from breast carcinoma diagnosis to lung carcinoma diagnosis. Using stratified analysis and unconditional logistic regression, the authors evaluated the main and combined effects of smoking and XRT on lung carcinoma risk.At the time of breast carcinoma diagnosis, 84% of case patients had ever smoked cigarettes, compared with 37% of control patients, whereas 45% of case patients and control patients received XRT for breast carcinoma. Smoking increased the odds of lung carcinoma in women without XRT (odds ratio [OR], 6.0; 95% confidence interval [95% CI], 3.6-10.1), but XRT did not increase lung carcinoma risk in nonsmoking women (OR, 0.5; 95% CI, 0.3-1.1). Overall, the OR for both XRT and smoking, compared with no XRT or smoking, was 9.0 (95% CI, 5.1-15.9). Logistic regression modeling yielded an adjusted OR of 5.6 for the smoking main effect (95% CI, 2.9-10.5), 0.6 for the XRT main effect (95% CI, 0.3-1.4), and 8.6 (P = 0.08) for the combined effect.Smoking was a significant independent risk factor for lung carcinoma after breast carcinoma, but XRT alone was not. Smoking and XRT combined enhanced the effect of either alone, with marked increased risks of lung carcinoma after XRT for breast carcinoma.

    View details for DOI 10.1002/cncr.11669

    View details for Web of Science ID 000185464100017

    View details for PubMedID 14508833

  • Untitled ANNALS OF EPIDEMIOLOGY Ness, R. B., Bondy, M. L., Branas, C., Camargo, C. A., Rothenberg, R., Samet, J. M., Sandler, D. P., Swanson, G. M., Strom, B. L. 2003; 13 (9): 597–98
  • Detection of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine-DNA adducts in normal breast tissues and risk of breast cancer CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Zhu, J. J., Chang, P., Bondy, M. L., Sahin, A. A., Singletary, S. E., Takahashi, S., Shirai, T., Li, D. H. 2003; 12 (9): 830–37

    Abstract

    2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), the most abundant heterocyclic amine (HCA) in cooked food, is a mammary carcinogen in female rats. In humans, consumption of well-done meat and PhIP intake have been associated with an increased risk of breast cancer, but PhIP-DNA adducts have not been analyzed in breast tissues from women having unknown exposure to HCAs. Using an immunohistochemistry (IHC) method, we measured PhIP-DNA adducts in normal breast tissues of 106 women having newly diagnosed breast cancer in comparison with those of 49 women undergoing reduction mammoplasty. The IHC method was first validated in MCF-7 cells treated with different doses of N-hydroxy-PhIP. We detected significant dose-response relationship and correlation (r=0.94) between the levels of PhIP-DNA adducts detected by IHC and 32P-postlabeling. Using IHC, PhIP-DNA adducts were detected in 82 and 71% of the normal breast tissue sections from the cancer and control patients respectively. The median (range) absorbance was 0.18 (0-0.57) and 0.08 (0-0.38) in the cancer and control patients, respectively (P<0.001). Using the median in the controls as a cutoff point, 71% of the cancer patients and 47% of the controls were distributed in the higher range (chi2=8.17; P=0.004). Logistic regression analysis demonstrated an OR of 4.03 (95% CI, 1.41-11.53) after adjusting for age and ethnicity (P=0.009). Stratified analyses did not find any significant effect of age, ethnicity, smoking, well-done meat consumption, dietary intake of PhIP, or polymorphisms of CYP1A1, CYP1B1, NAT2, and GSTM1 genes on the level of PhIP-DNA adducts. However, a potential interactive effect of well-done meat consumption and NAT2 genotype on the level of PhIP-DNA adducts was observed (P=0.047). This is the first study of detection of PhIP-DNA adducts in breast tissue samples obtained from women having unknown exposure to HCAs. These data strongly support the hypothesis that HCA exposure contributes to human breast cancer among genetically susceptible individuals.

    View details for Web of Science ID 000185467900003

    View details for PubMedID 14504191

  • Serum organochlorine levels and history of lactation in Egypt ENVIRONMENTAL RESEARCH Soliman, A. S., Wang, X. M., Di Giovanni, J., Eissa, S., Morad, M., Vulimiri, S., Mahgoub, K. G., Johnston, D. A., Do, K. A., Seifeldin, I. A., Boffetta, P., Bondy, M. L. 2003; 92 (2): 110–17

    Abstract

    We conducted a study in Egypt to assess the determinants of organochlorine serum levels among premenopausal women and the risk of premenopausal breast cancer for women with high organochlorine serum levels. We included 69 breast cancer patients and 53 controls consisting of visitors to the hospitals of the cancer patients. We found low levels of dichlorodiphenyldichloroethylene (DDE), total dichlorodiphenyltrichloroethane, and beta-hexacholorhexane (beta-HCH) in most subjects. Mean DDE levels were 12.7 +/- 20.3 ppb for cases and 16.6 +/- 30.1 ppb for controls (P = 0.60); beta-HCH levels were 2.1 +/- 3.8 ppb for patients and 2.1 +/- 3.9 ppb for controls (P = 0.71). Interestingly, subjects with low levels had breast fed their children for an average period of 18 months. Women with no lactation history had much higher organochlorine levels than women who breast fed (P = 0.002 for DDE). Younger age, older age at first childbirth, and shorter duration of breast feeding were significant predictors of higher levels of serum DDE levels. Younger age, older age at first childbirth, and higher body mass index were significant predictors of higher beta-HCH levels. This study suggests that organochlorine serum levels in Egyptian women are quite low, but indicates an effect of breast feeding in eliminating organochlorines, which would imply exposure to children. Organochlorine serum level was not a risk factor of breast cancer in this population.

    View details for DOI 10.1016/S0013-9351(02)00056-7

    View details for Web of Science ID 000183055700006

    View details for PubMedID 12854690

  • Molecular epidemiology of glioblastoma CANCER JOURNAL Aldape, K. D., Okcu, M. F., Bondy, M. L., Wrensch, M. 2003; 9 (2): 99–106

    Abstract

    Glioblastoma (GBM) is the most important primary brain tumor, both in terms of its incidence and its devastating impact on the unfortunate patients who have it. Although several well-defined hereditary syndromes predispose to malignant gliomas, most cases occur in the absence of a such a syndrome. The role of environmental factors, based on the known associations to date, also appears limited when compared with the total number of patients affected. It is clear that much remains to be discovered to better elucidate the causes of GBM, but the increasing recognition of molecular subtypes may help advance this field. This review highlights current insights into the molecular epidemiology of GBM.

    View details for DOI 10.1097/00130404-200303000-00005

    View details for Web of Science ID 000182892400005

    View details for PubMedID 12784875

  • Breast cancer risk assessment models: applicability to African-American women. Cancer Bondy, M. L., Newman, L. A. 2003; 97 (1 Suppl): 230–35

    Abstract

    BACKGROUND: Mortality rates are higher among African-American women with breast cancer than they are among white women. This population subset can benefit from available risk reduction strategies. Optimal public health gains from chemoprevention strategies depend on the ability to assess accurately the risk for the individual. However, it is not known if existing breast cancer prediction models are accurate predictors of the disease among African-American women.METHODS: Literature was reviewed for breast cancer risk prediction models and their validation studies. Reported data were also reviewed regarding the strength of established breast cancer risk factors for African-American women.RESULTS: The two currently accepted breast cancer risk assessment models, the Gail Model and the Claus Model, were designed primarily to provide risk assessments for white women. Neither model has been validated in African-American women. Reported data are inconsistent regarding the prevalence and strength of risk factors included in these models.CONCLUSIONS: Efforts should be made to validate existing risk assessment models in African-American women and future research should be directed at the identification of more reliable risk assessment features.

    View details for DOI 10.1002/cncr.11018

    View details for PubMedID 12491486

  • Epidemiology of primary brain tumors: Current concepts and review of the literature NEURO-ONCOLOGY Wrensch, M., Minn, Y., Chew, T., Bondy, M., Berger, M. S. 2002; 4 (4): 278-299

    Abstract

    The purpose of this review is to provide a sufficiently detailed perspective on epidemiologic studies of primary brain tumors to encourage multidisciplinary etiologic and prognostic studies among surgeons, neuro-oncologists, epidemiologists, and molecular scientists. Molecular tumor markers that predict survival and treatment response are being identified with hope of even greater gains in this area from emerging array technologies. Regarding risk factors, studies of inherited susceptibility and constitutive polymorphisms in genes pertinent to carcinogenesis (for example, DNA repair and detoxification genes and mutagen sensitivity) have revealed provocative findings. Inverse associations of the history of allergies with glioma risk observed in 3 large studies and reports of inverse associations of glioma with common infections suggest a possible role of immune factors in glioma genesis or progression. Studies continue to suggest that brain tumors might result from workplace, dietary, and other personal and residential exposures, but studies of cell phone use and power frequency electromagnetic fields have found little to support a causal connection with brain tumors; caveats remain. The only proven causes of brain tumors (that is, rare hereditary syndromes, therapeutic radiation, and immune suppression giving rise to brain lymphomas) account for a small proportion of cases. Progress in understanding primary brain tumors might result from studies of well-defined histologic and molecular tumor types incorporating assessment of potentially relevant information on subject susceptibility and environmental and noninherited endogenous factors (viruses, radiation, and carcinogenic or protective chemical exposures through diet, workplace, oxidative metabolism, or other sources). Such studies will require the cooperation of researchers from many disciplines.

    View details for Web of Science ID 000178161800006

    View details for PubMedID 12356358

    View details for PubMedCentralID PMC1920665

  • Maternal vitamin use and reduced risk of neuroblastoma EPIDEMIOLOGY Olshan, A. F., Smith, J. C., Bondy, M. L., Neglia, J. P., Pollock, B. H. 2002; 13 (5): 575–80

    Abstract

    Previous studies have suggested that maternal vitamin use during pregnancy may reduce the incidence of childhood brain tumors. Using data from a large North American study, we conducted an analysis to investigate maternal vitamin use and neuroblastoma in offspring.Cases were children diagnosed with neuroblastoma over the period 1 May 1992 to 30 April 1994 at Children's Cancer Group and Pediatric Oncology Group institutions throughout the United States and Canada. One matched control was selected for each case using random-digit dialing. We obtained vitamin use information during specific periods before and during pregnancy from 538 case and 504 control mothers through telephone interviews.Daily vitamin and mineral use in the month before pregnancy and in each trimester was associated with a 30-40% reduction in risk of neuroblastoma. For example, daily use in the second trimester had an odds ratio of 0.6 (95% confidence interval = 0.4-0.9). We were unable to isolate the effects of specific vitamins or minerals. Neither age at diagnosis nor oncogene amplification status materially altered the results.The results of this study suggest that vitamin use during pregnancy might reduce incidence of neuroblastoma, consistent with findings for other childhood cancers.

    View details for DOI 10.1097/00001648-200209000-00014

    View details for Web of Science ID 000177566700014

    View details for PubMedID 12192228

  • Dietary intake of selected fatty acids, cholesterol and carotenoids and estrogen receptor status in premenopausal breast cancer patients BREAST CANCER RESEARCH AND TREATMENT Jakovljevic, J., Touillaud, M. S., Bondy, M. L., Singletary, S. E., Pillow, P. C., Chang, S. 2002; 75 (1): 5–14

    Abstract

    Although a wealth of research has focused on the influence of diet on breast cancer risk, the relationships between dietary factors and tumor characteristics of breast cancer, like estrogen receptor (ER) status, are not well characterized. In a case-case study, we evaluated self-reported dietary intake for five individual carotenoids, selected fatty acids, and cholesterol 1 year before diagnosis in 34 premenopausal breast cancer patients with ER-negative tumors and 86 premenopausal breast cancer patients with ER-positive tumors from The University of Texas M. D. Anderson Cancer Center. In multivariate logistic regression analysis adjusted for age, body mass index, and ethnicity, high intakes of linoleic acid were associated with more than a threefold greater risk of ER-negative disease than ER-positive disease (odds ratio (OR) = 3.48, 95% confidence interval (CI) = 1.42-8.54), whereas high cholesterol intake was associated with lower risk of ER-negative disease (OR = 0.35, 95% CI = 0.14-0.92). In a model evaluating carotenoids, selected fatty acids, and cholesterol together, the association with high intake of linoleic acid remained statistically significant (OR = 3.96,95% CI = 1.53-10.25), while those for high intake of cholesterol (OR = 0.38, 95% CI = 0.14-1.03) and low intake of cryptoxanthin (OR = 0.43, 95% CI = 0.17-1.06) were of marginal significance. While no striking associations were observed for the intakes of total carotenoids, selected fatty acids, and cholesterol, our analysis revealed an association for the consumption of a specific fatty acid (i.e., linoleic acid), suggesting dietary influence of this factor on ER status in premenopausal breast cancer patients. However, larger studies are needed to clarify the role of micronutrients in ER status in breast cancer.

    View details for DOI 10.1023/A:1016588629495

    View details for Web of Science ID 000177099900002

    View details for PubMedID 12500930

  • Genetic and environmental determinants on tissue response to in vitro carcinogen exposure and risk of breast cancer CANCER RESEARCH Li, D. H., Walcott, F. L., Chang, P., Zhang, W. Q., Zhu, J. J., Petrulis, E., Singletary, S. E., Sahin, A. A., Bondy, M. L. 2002; 62 (16): 4566–70

    Abstract

    To test the hypothesis that individual susceptibility to carcinogen exposure is a risk factor for breast cancer, we measured DNA adduct formation in normal breast tissues treated in vitro with 4 micro M benzo(a)pyrene in 76 cancer cases and 60 noncancer controls. We found a significantly higher level of adducts (134.6 +/- 21.2/10(9)) among cases compared with controls (66.9 +/- 7.5; P = 0.007). The level of adducts was significantly associated with the risk of breast cancer (odds ratio, 4.38; 95% confidence interval, 1.04 to 18.50; P = 0.044) after adjusting for confounders. Stratified analysis and regression analysis demonstrated that race, pack-years of smoking, family history of breast cancer, and CYP1B1 genotype were significant predictors of the level of benzo(a)pyrene-induced adducts in the breast tissues. These observations suggest that genetic susceptibility to carcinogen exposure may play an important role in breast carcinogenesis.

    View details for Web of Science ID 000177496600008

    View details for PubMedID 12183407

  • A case-control study of unilateral and bilateral breast carcinoma patients. (vol 91, pg 1845, 2001) CANCER Newman, L. A., Sahin, A. A., Bondy, M. L., Mirza, N. Q., Vlastos, G. S., Whitman, G. J. 2002; 94 (4): 1191

    View details for DOI 10.1002/cncr.10484

    View details for Web of Science ID 000173907600039

  • Aromatic DNA adducts and polymorphisms of CYP1A1, NAT2, and GSTM1 in breast cancer CARCINOGENESIS Firozi, P. F., Bondy, M. L., Sahin, A. A., Chang, P., Lukmanji, F., Singletary, E. S., Hassan, M. M., Li, D. H. 2002; 23 (2): 301–6

    Abstract

    Previous studies by us and others have shown a significantly higher level of aromatic DNA adducts in normal adjacent breast tissue samples obtained from breast cancer patients than in those obtained from non-cancerous controls. The increased amount of DNA damage could be related to excess environmental carcinogen exposure and/or genetic susceptibility to such exposure. In the current study, we investigated the relationship between the levels of aromatic DNA adducts in breast tissues and polymorphisms of the drug-metabolizing genes cytochrome P4501A1 (CYP1A1), N-acetyltransferase-2 (NAT2), and glutathione S-transferase M1 (GSTM1), in 166 women having breast cancer. DNA adducts were measured using (32)P-postlabeling and information on smoking status was obtained from medical records. When pooled data of smokers and non-smokers were analyzed by multiple regression analyses, no significant correlation was found between the level of total DNA adducts and age, race, or polymorphisms of CYP1A1, GSTM1, and NAT2. The only significant predictor of the level of DNA adducts in breast tissues was smoking (P = 0.008). When data were analyzed separately in smokers and non-smokers, however, a significant gene-environment interaction was observed. Smokers with CYP1A1*1/*2 or *2/*2 genotypes had a significantly higher level of DNA adducts than those with the CYP1A1*1/*1 genotype. This effect was not seen among non-smokers. There was also a gene-gene interaction, as smokers with combined CYP1A1*1/*2 or CYP1A1*2/*2 genotypes and GSTM1 null had a much higher level of adducts than those with either CYP1A1 or GSTM1 polymorphism. Genetic polymorphisms of CYP1A1 and NAT2 were also significantly correlated with the frequency of certain types of DNA adducts. For example, a bulky benzo[a]pyrene (B[a]P)-like adduct was detected in 26% of the samples, the presence of which was not related to age, race, smoking status, or GSTM1 and NAT2 genotype. However, a significantly higher frequency of the B[a[P-like adduct was found in individuals having CYP1A1*1/*2 or *2/*2 genotypes than in those having the *1/*1 genotype (P = 0.04). In addition, individuals having slow NAT2 alleles had a significantly higher frequency of the typical smoking-related DNA adduct pattern, i.e. a diagonal radioactive zone (DRZ), than others did (P = 0.008). These findings suggest that polymorphisms of CYP1A1, GSTM1, and NAT2 significantly affect either the frequency or the level of DNA adducts in normal breast tissues of women having breast cancer, especially in smokers. Further large-scale studies are required to determine the exact role of these polymorphisms and types of DNA damage in breast cancer susceptibility.

    View details for DOI 10.1093/carcin/23.2.301

    View details for Web of Science ID 000174221700011

    View details for PubMedID 11872636

  • Knowledge and attitudes of Hispanic women and their health care providers about breast cancer risk factors and screening. Community genetics Strecker, M. N., Williams, A. J., Bondy, M., Johnston, D. A., Northrup, H. 2002; 5 (4): 222–31

    Abstract

    OBJECTIVES: The purpose of our study was to develop and evaluate an educational program for health care providers and patients on the topics of general breast cancer risk factors, breast cancer genetics, and breast cancer screening recommendations. The program was designed with specific emphasis on addressing the needs of medically underserved Hispanic women in Southern Texas. We also identified and compared perceptions of potential barriers to breast cancer screening.METHODS: The educational program was piloted with patient and health care provider focus groups. After incorporating modifications suggested by the focus groups, 103 patients and 94 health care providers (HCPs) from community health clinics in Harris County, Tex., were recruited to participate in the study. Changes in knowledge were measured through the use of pre- and postseminar questionnaires.RESULTS: The program identified various misconceptions about breast cancer in representative groups of patients and HCPs. Comparison of pre- and post-test scores indicated that both groups made significant gains in knowledge about breast cancer and breast cancer screening. Participant evaluations indicated that the seminar was informative and interesting. Both patients and HCPs agreed that the cost of breast cancer screening and the lack of sufficient bilingual HCPs were 'major' barriers to obtaining breast cancer screening, but had differing opinions regarding other potential barriers.CONCLUSIONS: We have developed an effective method of education about breast cancer risk factors and screening for two groups: Hispanic women of lower educational and socioeconomic levels, and the HCPs who serve them. Based on the successful reception of our program, we propose extending it to other areas of Texas with demographics similar to those of the study population.

    View details for DOI 10.1159/000066685

    View details for PubMedID 14960876

  • Unusually high rate of young-onset pancreatic cancer in the East Nile Delta region of Egypt JOURNAL OF GASTROINTESTINAL CANCER Soliman, A. S., El-Ghawalby, N., Ezzat, F., Bondy, M. L., Soultan, A., Abdel-Wahab, M., Fathy, O., Ebidi, G., Bassiouni, N., El-Ghawalbi, A., Levin, B., Abbruzzese, J. L. 2002; 32 (2-3): 143–51

    Abstract

    Pancreatic cancer is predominantly a disorder of the elderly population in the United States. In Egypt, the disease has traditionally been considered rare, and there has not been a previous publication on its population-based incidence or age distribution.We reviewed the records of 728 pancreatic cancer patients seen at the Gastrointestinal Surgery Center of Mansoura University in the East Nile Delta region of Egypt between 1995 and 2000. We computed population-based, age-specific, and age-adjusted incidence rates in this population and compared them with US incidence rates from the Epidemiology Surveillance and End Results (SEER) Program. We also analyzed clinical characteristics of the patients, as well as their surgical and medical management.Approximately one-fourth of all patients were under age 50. The mean ages of patients who had undergone Whipple's resection, other surgical procedures, and no surgical procedure were 52.9 +/- 11.6, 54.11 +/- 10.5, and 55.1 +/- 14.1 yr, with no statistically significant differences. Age-adjusted incidence rates were higher in Egyptian patients than in US patients under age 65 (7.1/100,000 vs 3.3/100,000) but were much higher in US patients than in Egyptian patients over age 65 (6.6/100,000 vs 59.1/100,000). Clinical management did not differ between patients under and over age 50.The population in the East Nile Delta region of Egypt exhibits an unusually high rate of young-onset pancreatic cancer. Further studies to investigate the epidemiology of pancreatic cancer in this population may provide clues to its etiology.

    View details for DOI 10.1385/IJGC:32:2-3:143

    View details for Web of Science ID 000184163400010

    View details for PubMedID 12794251

  • Sensitivity to benzo(a)pyrene diol-epoxide associated with risk of breast cancer in young women and modulation by glutathione S-transferase polymorphisms: A case-control study CANCER RESEARCH Xiong, P., Bondy, M. L., Li, D. H., Shen, H. B., Wang, L. E., Singletary, S. E., Spitz, M. R., Wei, Q. Y. 2001; 61 (23): 8465–69

    Abstract

    Mounting epidemiological evidence suggests that smoking may play a role in the etiology of breast cancer. Because smoking-related DNA adducts are detectable in both normal and malignant breast tissues, we hypothesized that breast cancer patients may be sensitive to tobacco-induced carcinogenesis, and this sensitivity could be modulated by variants of metabolic genes. To test this hypothesis, we evaluated benzo(a)pyrene diol-epoxide (BPDE)-induced mutagen sensitivity and polymorphisms of GSTM1 and GSTT1 in a pilot case-control study of breast cancer. Short-term cell cultures were established from blood samples of 100 female breast cancer patients and 105 healthy controls. After 5 h of in vitro exposure to 4 microM of BPDE, we harvested the lymphocytes for cytogenetic evaluation and recorded and compared the frequency of BPDE-induced chromatid breaks between cases and controls. We used a multiplex PCR-based assay to simultaneously detect polymorphisms of GSTM1 and GSTT1 from genomic DNA. We performed univariate and multivariate logistic regression analyses and calculated odds ratios (OR) and 95% confidence intervals (CIs). Cases had a significantly higher frequency of chromatid breaks than did controls (P < 0.0001). The level of chromatid breaks greater than the median value of controls was associated with a >3-fold increased risk of breast cancer [adjusted odds ratio (ORadj) = 3.11; 95% CI = 1.72-5.64]. The risk was more pronounced in those who were < 45 years (ORadj = 4.79; 95% CI = 1.87-12.3), ever-smokers (ORadj = 5.55; 95% CI = 1.85-16.6), alcohol drinkers (ORadj = 4.64; 95% CI = 1.70-12.7), and those who had the GSTT1 null variant (ORadj = 8.01; 95% CI = 1.16-55.3). These data suggest that sensitivity to BPDE-induced chromosomal aberrations may contribute to the risk of developing breast cancer, and such sensitivity may be modulated by both genetic and environmental factors. Larger studies are needed to confirm our findings.

    View details for Web of Science ID 000172594600023

    View details for PubMedID 11731429

  • Evaluation of Mexican American migrant farmworker work practices and organochlorine pesticide metabolites AMERICAN JOURNAL OF INDUSTRIAL MEDICINE Hernandez-Valero, M. A., Bondy, M. L., Spitz, M. R., Zahm, S. H. 2001; 40 (5): 554–60

    Abstract

    Epidemiologic studies often must rely upon questionnaire data to assess past exposures. The ability of questionnaires to rank migrant farmworkers according to past pesticide exposure is not known.We conducted a pilot feasibility study to measure a panel of 21 organochlorine pesticides (OCPs) and correlate levels with reported occupational exposures in 26 Mexican-American migrant farmworkers in Baytown, Texas. The Migrant Farmworker Questionnaire developed by the National Cancer Institute (NCI) was administered and each participant donated a blood sample. Three OCPs [mean (ppb) levels: mirex 1.8, DDT 1.0, and trans-nonachlor 0.7] were detected despite the fact that these chemicals have been banned in the US for many years, and the detected levels were far higher than the standard provided by the referent laboratory. Work clothes, protective attire, and self-reported pesticide exposures were significant predictors of OCP exposure. Similarly, personal hygiene, length of employment, and number of duties also predicted OCP exposure.The results of this study indicate that data obtained from standardized questionnaires may be reasonable indicators of occupational exposure when biomarker data are not available.

    View details for DOI 10.1002/ajim.10008

    View details for Web of Science ID 000172062900008

    View details for PubMedID 11675624

  • gamma-radiation sensitivity and risk of glioma JOURNAL OF THE NATIONAL CANCER INSTITUTE Bondy, M. L., Wang, L. E., El-Zein, R., de Andrade, M., Selvan, M. S., Bruner, J. M., Levin, V. A., Yung, W. K., Adatto, P., Wei, Q. Y. 2001; 93 (20): 1553–57

    Abstract

    About 9% of human cancers are brain tumors, of which 90% are gliomas. gamma-Radiation has been identified as a risk factor for brain tumors. In a previous pilot study, we found that lymphocytes from patients with glioma were more sensitive to gamma-radiation than were lymphocytes from matched control subjects. In this larger case-control study, we compared the gamma-radiation sensitivity of lymphocytes from glioma patients with those from control subjects and investigated the association between mutagen sensitivity and the risk for developing glioma.We used a mutagen sensitivity assay (an indirect measure of DNA repair activity) to assess chromosomal damage. We gamma-irradiated (1.5 Gy) short-term lymphocyte cultures from 219 case patients with glioma and from 238 healthy control subjects frequency matched by age and sex. After irradiation, cells were cultured for 4 hours, and then Colcemid was added for 1 hour to arrest cells in mitosis. Fifty metaphases were randomly selected for each sample and scored for chromatid breaks. All statistical tests were two-sided.We observed a statistically significantly higher frequency of chromatid breaks per cell from case patients with glioma (mean = 0.55; 95% confidence interval [CI] = 0.50 to 0.59) than from control subjects (mean = 0.44; 95% CI = 0.41 to 0.48) (P<.001). Using 0.40 (the median number of chromatid breaks per cell in control subjects) as the cut point for defining mutagen sensitivity and adjusting for age, sex, and smoking status, we found that mutagen sensitivity was statistically significantly associated with an increased risk for glioma (odds ratio = 2.09; 95% CI = 1.43 to 3.06). When the data were divided into tertiles, the relative risk for glioma increased from the lowest tertile to the highest tertile (trend test, P<.001).gamma-Radiation-induced mutagen sensitivity of lymphocytes may be associated with an increased risk for glioma, a result that supports our earlier preliminary findings.

    View details for DOI 10.1093/jnci/93.20.1553

    View details for Web of Science ID 000171535000011

    View details for PubMedID 11604478

  • Contrasting molecular pathology of colorectal carcinoma in Egyptian and Western patients BRITISH JOURNAL OF CANCER Soliman, A. S., Bondy, M. L., El-Badawy, S. A., Mokhtar, N., Eissa, S., Bayoumy, S., Seifeldin, I. A., Houlihan, P. S., Lukish, Watanabe, T., Chan, A. O., Zhu, D., Amos, C. I., Levin, B., Hamilton 2001; 85 (7): 1037–46

    Abstract

    Colorectal carcinoma is uncommon in Egypt, but a high proportion of cases occurs before age 40 years and in the rectum. We compared the molecular pathology of 59 representative Egyptian patients aged 10-72 to Western patients with sporadic, young-onset, or hereditary non-polyposis colorectal cancer syndrome (HNPCC)-associated carcinoma and found significant differences. Most Egyptian cancers were rectal (51%) and poorly differentiated (58%). High levels of microsatellite instability (MSI-H) were frequent (37%) and attributable in some cases (36%) to methylation of the promoter of the hMLH1 mismatch repair gene, but no MSI-H cancer had loss of hMSH2 mismatch repair gene product of the type seen with germline hMSH2 mutation in HNPCC. K-ras mutation was uncommon (11%). In subset analyses, high frequencies of MSI-H in rectal carcinomas (36%) and p53 gene product overexpression in MSI-H cancers (50%) were found. MSI-H and K-ras mutation in Egyptians under age 40 were unusual (17% and 0%, respectively), and schistosomiasis was associated with MSI and K-ras mutation. Cluster analysis identified 2 groups: predominantly young men with poorly differentiated mucinous and signet-ring cell colorectal carcinoma lacking K-ras mutation; older patients who had well- or moderately differentiated adenocarcinoma often with MSI-H, K-ras mutation and schistosomiasis. Our findings show that the molecular pathology of colorectal cancer in older as well as younger Egyptians has unique differences from Western patients, and schistosomiasis influences the molecular pathogenesis of some tumours.

    View details for DOI 10.1054/bjoc.2001.1838

    View details for Web of Science ID 000171685300017

    View details for PubMedID 11592777

    View details for PubMedCentralID PMC2375101

  • Oxidative DNA damage and 8-hydroxy-2-deoxyguanosine DNA glycosylase/apurinic lyase in human breast cancer MOLECULAR CARCINOGENESIS Li, D. H., Zhang, W. Q., Zhu, J. J., Chang, P., Sahin, A., Singletary, E., Bondy, M., Mitra, S., Lau, S. S., Shen, J. J., DiGiovanni, J. 2001; 31 (4): 214–23

    Abstract

    To test the hypothesis that oxidative stress is involved in breast cancer, we compared the levels of 8-hydroxy-2-deoxyguanosine (8-oxo-dG), an oxidized DNA base common in cells undergoing oxidative stress, in normal breast tissues from women with or without breast cancer. We found that breast cancer patients (N = 76) had a significantly higher level of 8-oxo-dG than control subjects (N = 49). The mean ( +/- SD) values of 8-oxo-dG/10(5) dG, as measured by high-performance liquid chromatography electrochemical detection, were 10.7 +/- 15.5 and 6.3 +/- 6.8 for cases and controls, respectively (P = 0.035). This difference also was found by immunohistochemistry with double-fluorescence labeling and laser-scanning cytometry. The average ratios (x10(6)) of the signal intensity of antibody staining to that of DNA content were 3.9 +/- 7.2 and 1.1 +/- 1.4 for cases (N = 57) and controls (N = 34), respectively (P = 0.008). There was no correlation between the ages of the study subjects and the levels of 8-oxo-dG. Cases also had a significantly higher level of 8-hydroxy-2-deoxyguanosine DNA glycosylase/apurinic lyase (hOGG1) protein expression in normal breast tissues than controls (P = 0.008). There was no significant correlation between hOGG1 expression and 8-oxo-dG. Polymorphism of the hOGG1 gene was very rare in this study population. The previously reported exon 1 polymorphism and two novel mutations of the hOGG1 gene were found in three of 168 cases and two of 55 controls. In conclusion, normal breast tissues from cancer patients had a significantly higher level of oxidative DNA damage. The elevated level of 8-oxo-dG in cancer patients was not related to age or to deficiency of the hOGG1 repair gene.

    View details for DOI 10.1002/mc.1056

    View details for Web of Science ID 000170874900005

    View details for PubMedID 11536371

  • Parental occupational exposures to chemicals and incidence of neuroblastoma in offspring AMERICAN JOURNAL OF EPIDEMIOLOGY De Roos, A. J., Olshan, A. F., Teschke, K., Poole, C., Savitz, D. A., Blatt, J., Bondy, M. L., Pollock, B. H. 2001; 154 (2): 106–14

    Abstract

    To evaluate the effects of parental occupational chemical exposures on incidence of neuroblastoma in offspring, the authors conducted a multicenter case-control study, using detailed exposure information that allowed examination of specific chemicals. Cases were 538 children aged 19 years who were newly diagnosed with confirmed neuroblastoma in 1992-1994 and were registered at any of 139 participating hospitals in the United States and Canada. One age-matched control for each of 504 cases was selected through random digit dialing. Self-reported exposures were reviewed by an industrial hygienist, and improbable exposures were reclassified. Effect estimates were calculated using unconditional logistic regression, adjusting for child's age and maternal demographic factors. Maternal exposures to most chemicals were not associated with neuroblastoma. Paternal exposures to hydrocarbons such as diesel fuel (odds ratio (OR) = 1.5; 95% confidence interval (CI): 0.8, 2.6), lacquer thinner (OR = 3.5; 95% CI: 1.6, 7.8), and turpentine (OR = 10.4; 95% CI: 2.4, 44.8) were associated with an increased incidence of neuroblastoma, as were exposures to wood dust (OR = 1.5; 95% CI: 0.8, 2.8) and solders (OR = 2.6; 95% CI: 0.9, 7.1). The detailed exposure information available in this study has provided additional clues about the role of parental occupation as a risk factor for neuroblastoma.

    View details for DOI 10.1093/aje/154.2.106

    View details for Web of Science ID 000169906400002

    View details for PubMedID 11447042

  • A case-control study of unilateral and bilateral breast carcinoma patients CANCER Newman, L. A., Sahin, A. A., Bondy, M. L., Mirza, N. Q., Vlastos, G. S., Whitman, G. J., Brown, H., Buchholz, T. A., Lee, M. H., Singletary, S. E. 2001; 91 (10): 1845–53

    Abstract

    Women with unilateral breast carcinoma are at increased risk for developing contralateral disease. The clinical significance of bilateral breast carcinoma has not been fully defined, and the subset of patients who may benefit from medical or surgical risk-reduction intervention has not yet been characterized. The purpose of this study was to evaluate risk factors and outcomes for bilateral breast carcinoma.A subject group of 70 bilateral breast carcinoma patients (62% metachronous) was matched by age and survival interval with a control group of 70 unilateral breast carcinoma patients. Median follow-up was 103 months.Eighty-two percent of the unilateral patients and 80% of the bilateral patients had Stage I or II disease at diagnosis. Median age at presentation was 53 years. In the bilateral group, the contralateral cancer was diagnosed at the same or earlier stage than the first cancer in 87% of cases. Bilateral patients were significantly more likely to have multicentric disease and to have a positive family history for breast carcinoma compared with the unilateral group. There were no significant differences regarding history of exogenous hormone exposure, lobular histology, hormone-receptor status, or HER-2/neu expression. Five-year disease-free survival was 94% for the unilateral breast carcinoma patients and 91% for the bilateral breast carcinoma patients (P = 0.16).Survival for patients with bilateral breast carcinoma is similar to that of patients with unilateral disease; however, prophylactic risk-reduction intervention for the contralateral breast should be considered in patients who have multicentric unilateral disease or a positive family history for breast carcinoma.

    View details for DOI 10.1002/1097-0142(20010515)91:10<1845::AID-CNCR1205>3.0.CO;2-Z

    View details for Web of Science ID 000168497900001

    View details for PubMedID 11346865

  • Familial aggregation of colorectal cancer in Egypt is not related to HNPCC Soliman, A. S., Abdel-Karim, N., Bondy, M. L., El-Serafi, M., El-Badawy, S., Amos, C. I., Hamilton, Levin, B. W B SAUNDERS CO. 2001: A740
  • Correlation of p27 protein expression with HER-2/neu expression in breast cancer MOLECULAR CARCINOGENESIS Newman, L., Xia, W. Y., Yang, H. Y., Sahin, A., Bondy, M., Lukmanji, F., Hung, M. C., Lee, M. H. 2001; 30 (3): 169–75

    Abstract

    Strong expression of human epidermal growth factor receptor 2 (HER-2)/neu in breast cancer has been associated with poor prognosis. Reduced expression of p27(Kip1), a cyclin-dependent kinase inhibitor, correlates with poor clinical outcome in breast cancer. In this study, we provide a correlation between these two important prognostic markers in patients with breast cancer. Breast tumor screening using immunohistochemistry indicated that downregulation of p27 correlated with HER-2/neu overexpression in studying 11 normal breast tissues and 51 primary breast carcinomas. We found HER-2/neu protein overexpression in 20 (41%) of 49 breast cancers and low p27 protein expression in 47 (92%) of 51 breast cancers. All 20 (100%) of the tumors that overexpressed HER-2/neu had low levels of p27 protein product; this correlation was statistically significant (P = 0.035). Decreasing p27 expression correlated with increasing HER-2/neu activity. Our results suggest that one function of the HER-2/neu product is to downregulate p27 expression in breast cancer. This study may be significant in selecting patients for HER-2/neu antibody therapy in the future. Mol. Carcinog. 30:169--175, 2001.

    View details for DOI 10.1002/mc.1025

    View details for Web of Science ID 000167964800005

    View details for PubMedID 11301477

  • Segregation analysis of cancer in families of glioma patients GENETIC EPIDEMIOLOGY de Andrade, M., Barnholtz, J. S., Amos, C. I., Adatto, P., Spencer, C., Bondy, M. L. 2001; 20 (2): 258–70

    Abstract

    A small proportion of brain tumors are attributed to a genetic predisposition; however, the hereditary proportion is undetermined. This study evaluates the degree of familial aggregation of cancer in a large series of brain tumor patients. Our study included 5,088 relatives of 639 probands (3,810 first- and 1,278 second-degree), diagnosed with a glioma between June 1992 and June 1995 at The University of Texas M. D. Anderson Cancer Center, Houston, Texas, with diagnosis under age 65 years, and residents of the United States or Canada. We conducted an in-person or telephone interview with patients and/or their next-of-kin, and obtained family histories for the probands' first-degree (parents, siblings, offspring) and selected second-degree relatives (aunts, uncles, grandparents) using a sequential sampling strategy. Reported cancers were documented by medical records and/or death certificates (if the relative was deceased and medical records were unavailable). We conducted segregation analysis using the Pedigree Analysis Program (PAP). The analyses were divided into two categories: (1) all 639 families, and (2) a subset of families whose gliomas stained positive on p53 immunohistochemistry analysis. We demonstrated that a multifactorial Mendelian model was favored, while a model postulating a purely environmental cause of brain cancer was rejected. This study indicates that familial cancer in relatives of glioma patients are probably a result of multigenic action, and familial clustering of cancer among relatives of glioma patients may involve unknown environmental exposures.

    View details for DOI 10.1002/1098-2272(200102)20:2<258::AID-GEPI8>3.0.CO;2-N

    View details for Web of Science ID 000166634300008

    View details for PubMedID 11180451

  • Risk assessment for developing gliomas: a comparison of two cytogenetic approaches MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS El-Zein, R., Bondy, M. L., Wang, L. E., de Andrade, M., Sigurdson, A. J., Bruner, J. M., Kyritsis, A. P., Levin, V. A., Wei, Q. Y. 2001; 490 (1): 35–44

    Abstract

    Chromosome instability (CIN) measured as chromosome aberrations has long been suggested as a cancer susceptibility biomarker. Conventional cytogenetic end-points are now being improved by combining molecular methods, which increases the sensitivity, specificity, and precision of the assay. In this study we examined both spontaneous and gamma-ray induced CIN in lymphocyte cultures from 51 previously untreated glioma patients and 51 age-, sex- and ethnicity-matched controls. CIN was assessed using two parallel methods: (1) the mutagen sensitivity (MS) assay and (2) the multicolor fluorescence in situ hybridization (FISH) assay. The frequency of spontaneous breaks was significantly higher in glioma patients (mean+/-S.D., 2.12+/-1.07) than in controls (1.24+/-0.86, P<0.001) when using the FISH assay but not the MS assay (0.019+/-0.02 and 0.019+/-0.01, respectively; P=0.915). Similarly, the frequency of induced chromatid breaks was significantly higher using the FISH assay (3.39+/-1.72) but not the MS assay (0.42+/-0.16) in the patients versus controls (2.08+/-1.18 and 0.37+/-0.15, respectively; P<0.001 and P=0.10, respectively). By using the median number of breaks in the controls as the cutoff value, we observed an odds ratio (ORs) of 5.13 (95% CI=2.23-12.1) for spontaneous and 4.86 (95% CI=2.08-11.4) for induced CIN using the FISH assay, whereas the ORs were 1.32 (95% CI=0.49-3.58) and 1.28 (95% CI=0.59-2.80) for spontaneous and induced CIN using the MS assay. There was also a significant increase in the frequency of hyperdiploid cells in the glioma cases which could only be detected using the FISH assay (OR=4.0, 95% CL=0.9-17.0). By combining both methods an estimated risk of 7.0 (95% CI=1.7-25.6) was observed. There was no correlation between the breaks detected by the two methods suggesting that each method is a measure of a different event. The results indicate that using the multicolor FISH assay for detection of CIN in peripheral blood lymphocytes in glioma patients is a more useful marker for risk assessment.

    View details for DOI 10.1016/S1383-5718(00)00154-6

    View details for Web of Science ID 000166729600005

    View details for PubMedID 11152970

  • Residential pesticide exposure and neuroblastoma EPIDEMIOLOGY Daniels, J. L., Olshan, A. F., Teschke, K., Hertz-Picciotto, Savitz, D. A., Blatt, J., Bondy, M. L., Neglia, J. P., Pollock, B. H., Cohn, S. L., Look, A. T., Seeger, R. C., Castleberry, R. P. 2001; 12 (1): 20–27

    Abstract

    Neuroblastoma is the most common neoplasm in children under 1 year of age. We examined the relation between residential exposure to pesticides and neuroblastoma, using data from a case-control study of risk factors for neuroblastoma. Incident cases of neuroblastoma (N = 538) were identified through the Pediatric Oncology Group and the Children's Cancer Group. One age-matched control was identified for each case by random digit dialing. Telephone interviews with each parent collected information on residential exposure to pesticides. Pesticide use in both the home and garden were modestly associated with neuroblastoma [odds ratio (OR) = 1.6 (95% confidence interval [95% CI] = 1.0-2.3, and OR = 1.7 (95% CI = 0.9-2.1), respectively]. Compared with infants [OR = 1.0 (95% CI = 0.6-2.0)], stronger associations were found for garden pesticides in children diagnosed after 1 year of age [OR = 2.2 (95% CI = 1.3-3.6)], which suggests that pesticides may act through a mechanism more common for neuroblastomas in older children. There was no evidence of differential pesticide effects in subgroups of neuroblastoma defined by MYCN oncogene amplification or tumor stage.

    View details for DOI 10.1097/00001648-200101000-00005

    View details for Web of Science ID 000166006400005

    View details for PubMedID 11138814

  • Neoplasms in neurofibromatosis 1 are related to gender but not to family history of cancer GENETIC EPIDEMIOLOGY Airewele, G. E., Sigurdson, A. J., Wiley, K. J., Frieden, B. E., Caldarera, L. W., Riccardi, V. M., Lewis, R. A., Chintagumpala, M. M., Ater, J. L., Plon, S. E., Bondy, M. L. 2001; 20 (1): 75–86

    Abstract

    The risk of malignancies among persons with neurofibromatosis 1 (NF1) is higher than in the general population, but the excess risk has not been precisely estimated. The effects of gender and inheritance pattern on cancer risk are unclear. Therefore, we conducted a historical cohort study to determine cancer risk factors by contacting 138 Caucasian NF1 patients originally seen at Baylor College of Medicine (BCM) in Houston between 1978 and 1984. A total of 304 patients of all ethnic groups were evaluated at BCM during this period. We successfully located 173 patients, 138 of who were Caucasian. We computed standardized incidence ratios (SIRs) with the age-, gender-, and time period-specific rates from the Connecticut Tumor Registry for 2,094 person-years of observation (median follow-up = 16 years). Eleven incident tumors were reported. Females were at much higher risk of cancer than males (SIR = 5.6, 95% confidence interval (CI) 2.7-10.3 and SIR = 0.6; 95% CI, 0.0-3.0, respectively). We found no elevated cancer risk in unaffected first-degree relatives, regardless of whether the proband had cancer or not (SIR = 1.1 95% CI, 0.6-1.8 and SIR = 1.0, 95% CI, 0.6-1.5, respectively). Our results suggest that malignancy in the proband is not the result of a modifying gene that has a significant impact on general cancer risk.

    View details for DOI 10.1002/1098-2272(200101)20:1<75::AID-GEPI7>3.0.CO;2-Z

    View details for Web of Science ID 000165982700007

    View details for PubMedID 11119298

  • Patterns of expression of Rb and p16 in astrocytic gliomas, and correlation with survival INTERNATIONAL JOURNAL OF ONCOLOGY Puduvalli, V. K., Kyritsis, A. P., Hess, K. R., Bondy, M. L., Fuller, G. N., Kouraklis, G. P., Levin, V. A., Bruner, J. M. 2000; 17 (5): 963–69

    Abstract

    The retinoblastoma pathway is a key cell cycle regulatory complex that controls the passage of cells through the G1 checkpoint and is a frequent target of genetic alterations in gliomas. In this study, we examined the expression of Rb and p16 in 170 primary astrocytic gliomas by immunohistochemical techniques, and correlated the expression with overall survival to determine their prognostic value as immunomarkers. There were 130 patients with glioblastoma multiforme (GBM) and 40 with anaplastic astrocytoma (AA). Alterations in the levels of Rb or p16 expression were seen in the majority (>90%) of the gliomas studied. The expression of Rb was completely absent or low in 47.5% of the GBM and 67.5% of the AA. The remainder of the tumors was immunopositive for Rb to varying degrees. Immunoreactivity for p16 was absent in 56% of the GBM and 77.5% of the AA. Kaplan-Meier survival plots (log-rank test) and Cox proportional hazards regression analysis, adjusted for age and histology, showed that neither Rb nor p16 expression independently predicted survival. The results of our study suggest that although genetic alterations of Rb and p16 are common in gliomas, immunohistochemical analysis of these markers correlates poorly with prognosis.

    View details for Web of Science ID 000089825300014

    View details for PubMedID 11029499

  • Inheritance of the 194Trp and the 399Gln variant alleles of the DNA repair gene XRCC1 are associated with increased risk of early-onset colorectal carcinoma in Egypt CANCER LETTERS Abdel-Rahman, S. Z., Soliman, A. S., Bondy, M. L., Omar, S., El-Badawy, S. A., Khaled, H. M., Seifeldin, I. A., Levin, B. 2000; 159 (1): 79–86

    Abstract

    Patients under age 40 constitute 35.6% of all colorectal cancer cases in Egypt, an unusual disease pattern to which both environmental exposures and inefficient DNA repair may contribute. While a number of polymorphisms in DNA repair genes have been recently identified, their role as cancer risk modifiers is yet to be determined. In a pilot case-control study, we tested the hypothesis that polymorphisms in the gene for the DNA repair enzyme XRCC1 are associated with increased risk of colorectal cancer among Egyptians. Using a multiplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology, allelic variants of the XRCC1 gene at codons 194 (Arg-->Trp) (194Trp) and 399 (Arg-->Gln) (399Gln), were analyzed in DNA from lymphocytes of 48 newly-diagnosed colorectal cancer cases and 48 age- and sex-matched controls. Overall, the inheritance of 194Trp allele (Arg/Trp genotype) and 399Gln allele (combined Arg/Gln and Gln/Gln genotypes) was associated with increased colorectal cancer risk (odds ratio (OR)=2.56, 95% confidence limits (CL) 0.73-9.40, and P=0. 08 for 194Trp allele and OR=3.98, 95% CL 1.50-10.6, and P<0.001 for 399Gln allele). Interestingly, the frequencies of 194Trp and 399Gln genotypes were higher in colorectal cancer cases under age 40 than in corresponding controls, and an association between both polymorphisms and early age of disease onset was observed (OR=3.33, 95% CL 0.48-35.90, and P=0.16 for 194Trp and OR=11.90, 95% CL 2.30-51.50, and P=0.0003 for 399Gln). Analysis of the data after adjustment for place of residence indicated that the frequencies of the genotypes with the 194Trp and the 399Gln alleles were higher among urban residents (OR=3.33, 95% CL 0.48-35.90, and P=0.16 for 194Trp and OR=9.97, 95% CL 1.98-43.76, and P<0.001 for 399Gln) than among rural residents (OR=2.00, 95% CL 0.36-26.00, and P=0.30 for 194Trp and OR=1.90, 95% CL 0.50-7.53, and P=0.20 for 399Gln). These findings support our hypothesis and suggest that polymorphisms in the XRCC1 gene, in conjunction with place of residence, may modify disease risk. This first demonstration that polymorphisms in DNA repair genes may contribute to colorectal cancer susceptibility and may increase the risk of early onset of the disease opens the door for future studies in that direction.

    View details for DOI 10.1016/S0304-3835(00)00537-1

    View details for Web of Science ID 000166663300011

    View details for PubMedID 10974409

  • Parental smoking and alcohol consumption and risk of neuroblastoma CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Yang, Q. H., Olshan, A. F., Bondy, M. L., Shah, N. R., Pollock, B. H., Seeger, R. C., Look, A. T., Cohn, S. L. 2000; 9 (9): 967–72

    Abstract

    Previous studies and animal evidence have suggested a relationship between parental tobacco or alcohol use and the risk of some childhood cancers, including neuroblastoma. A case-control study was conducted to investigate the relationship between parental tobacco smoking, alcohol consumption, and risk of neuroblastoma. Cases were children diagnosed with neuroblastoma over the period 1992-1994 at Children's Cancer Group and Pediatric Oncology Group institutions throughout the United States and Canada. One matched control was selected using random-digit dialing. Information on parental smoking and drinking history was obtained from 504 case and 504 control parents by telephone interview. Overall, there was no consistent pattern of association with parental smoking and alcohol consumption. For example, both maternal smoking and drinking during the period from 1 month before pregnancy through breastfeeding had adjusted odds ratios (ORs) of 1.1 [95% confidence interval (CI), 0.8-1.4]. There was no association with paternal smoking (OR, 1.2; 95% CI, 0.8-1.6) or paternal drinking 1 month before conception (OR, 1.0; 95% CI, 0.7-1.4). There was no consistent increase in risk by the amount of smoking or drinking during any time period relative to pregnancy. There was no suggestion of an increased risk when only one parent smoked. Smoking or drinking among both parents did not jointly increase the risk of neuroblastoma in their offspring. The child's age at diagnosis, stage, or MYCN oncogene amplification status did not materially alter the OR estimates. It is concluded that the results from this study do not indicate any evidence for a relationship between neuroblastoma and parental tobacco or alcohol use.

    View details for Web of Science ID 000089392600016

    View details for PubMedID 11008916

  • Gender difference in smoking effect on chromosome sensitivity to gamma radiation in a healthy population RADIATION RESEARCH Wang, L. E., Bondy, M. L., de Andrade, M., Strom, S. S., Wang, X. Z., Sigurdson, A., Spitz, M. R., Wei, Q. Y. 2000; 154 (1): 20–27

    Abstract

    In the general population, there is variation in radiosensitivity associated with cancer risk. However, data on the role of epigenetic factors in the variation of radiosensitivity are scarce. Thus we investigated the effects of smoking and age on the radiosensitivity of human lymphocytes by measuring the frequency of chromosome aberrations after in vitro exposure to gamma rays in peripheral lymphocytes from 441 healthy subjects (18-95 years old). We analyzed the frequency of both spontaneous (baseline) and in vitro gamma-ray-induced (1.5 Gy) chromatid breaks in 50 well-spread metaphases per subject. The overall mean frequencies of spontaneous and induced breaks were 0.02 and 0.45 per cell, respectively. The mean frequency of induced breaks was significantly higher in men than in women (P = 0.03) but did not differ by age or ethnicity. Donors who had ever smoked showed a small but significantly increased frequency of induced breaks (mean = 0.47) compared to nonsmokers (mean = 0.41; P = 0.005). Further stratification and multivariate analyses revealed that the smoking effect was more pronounced in men than in women. These findings support a smoking effect on radiosensitivity in a healthy population, particularly in men. Therefore, when evaluating the association between radiosensitivity and susceptibility to smoking-related cancers, the effect of smoking should be taken into account.

    View details for DOI 10.1667/0033-7587(2000)154[0020:GDISEO]2.0.CO;2

    View details for Web of Science ID 000087861700004

    View details for PubMedID 10856961

  • Contrasting epidemiology and molecular pathology of colorectal carcinoma in Egyptian and western patients. Soliman, A. S., Bondy, M. L., Mokhtar, N., Bayomy, S., Houlihan, P. S., Longo, P. A., Lukish, Watanabe, T., Amos, C., Levin, B., Hamilton, S. W B SAUNDERS CO. 2000: A756–A757
  • Hormone and fertility drug use and the risk of neuroblastoma: A report from the Children's Cancer Group and the Pediatric Oncology Group AMERICAN JOURNAL OF EPIDEMIOLOGY Olshan, A. F., Smith, J., Cook, M. N., Grufferman, S., Pollock, B. H., Stram, D. O., Seeger, R. C., Look, A. T., Cohn, S. L., Castleberry, R. P., Bondy, M. L. 1999; 150 (9): 930–38

    Abstract

    Previous epidemiologic studies have suggested an association between maternal sex hormone use during pregnancy, including infertility medication, and an increased risk of neuroblastoma in the offspring. The authors conducted a case-control interview study from 1992 to 1996 that included 504 children less than 19 years of age whose newly diagnosed neuroblastoma was identified by two national collaborative clinical trials groups in the United States and Canada, the Children's Cancer Group and the Pediatric Oncology Group. Controls, matched to cases on age, were identified by random digit dialing. No association was found for use of oral contraceptives before or during pregnancy (first trimester odds ratio (OR) = 1.0, 95% confidence interval (CI): 0.5, 2.1). The odds ratio was slightly elevated for history of infertility (OR = 1.4, 95% CI: 0.9, 2.1) and ever use of any infertility medication (OR = 1.2, 95% CI: 0.7, 2.2). Specifically, ever use of clomiphene was associated with a 1.6-fold increased risk (95% CI: 0.8, 3.0) but not periconceptionally or during the index pregnancy. A suggestive pattern was found for gender of the offspring, with an increased risk for males but not for females after exposure to oral contraceptives or clomiphene. This study did not find consistent and large increased risks for maternal use of hormones, but the suggestion of an association for male offspring requires further consideration.

    View details for Web of Science ID 000083468000005

    View details for PubMedID 10547138

  • Cancer mortality in Menofeia, Egypt: comparison with US mortality rates CANCER CAUSES & CONTROL Soliman, A. S., Bondy, M. L., Raouf, A. A., Makram, M. A., Johnston, D. A., Levin, B. 1999; 10 (5): 349–54

    Abstract

    In developing countries where cancer registries are unavailable, mortality statistics from death certification may be a practical source of cancer statistics. We aimed at describing the cancer mortality in Egypt and comparing it to that in the US.We used the mandatory and routinely available mortality records of Menofeia province in the Nile Delta region of Egypt, which is typical of the rest of Egypt. We determined cancer mortality rates, and compared them with the Surveillance, Epidemiology, and End Results (SEER) mortality rates of the US.Bladder and liver cancers were the two most common causes of cancer mortality in Menofeia, Egypt. When adjusted for age the Egyptian rates were much higher than the US rates (9.5/100,000 and 8.4/100,000 for bladder and liver cancer, respectively, compared with 2.3/100,000 and 2.5/100,000 for the same cancers from SEER data). We also observed that age-specific rates for early-onset colorectal cancer under age 40 and premenopausal breast cancer were higher in Egypt than in the US.This study confirms our earlier observations about the higher proportion of early-onset colorectal cancer in Egypt, and opens the door for future studies to investigate familial clustering of cancer in Egypt.

    View details for DOI 10.1023/A:1008968701313

    View details for Web of Science ID 000082676100005

    View details for PubMedID 10530604

  • Knowledge and attitudes of Hispanic women and their health care providers about breast cancer risk factors and screening. Strecker, M. N., Tucker, A. J., Bondy, M. L., Johnston, D. A., Northrup, H. UNIV CHICAGO PRESS. 1999: A388
  • Lung cancer after breast cancer: The role of radiation therapy and smoking Ford, M. B., Sigurdson, A. J., Stewart, S. E., Ng, C., Cooksley, C., Kemp, B., McNeese, M., deAndrade, M., Spitz, M. R., Bondy, M. L. PERGAMON-ELSEVIER SCIENCE LTD. 1999: S248
  • Polymorphism of glutathione S-transferase loci GSTM1 and GSTT1 and susceptibility to colorectal cancer in Egypt CANCER LETTERS Abdel-Rahman, S. Z., Soliman, A. S., Bondy, M. L., Wu, X. F., El-Badawy, S. A., Mahgoub, K. G., Ismail, S., Seifeldin, I. A., Levin, B. 1999; 142 (1): 97–104

    Abstract

    Egypt has an unusually high proportion of early-onset colorectal cancer under age 40 years. Environmental exposures and low DNA repair capacity are among the risk factors. Because GSTM1 and GSTT1 gene deficiencies may act as risk modifiers for colorectal cancer risk, we investigated the relationship between genetic polymorphism in these genes and colorectal cancer risk in Egyptians. Sixty-six patients and 55 controls were included. Genotyping for GSTM1 and GSTT1 was conducted using PCR techniques and the results were related to epidemiologic and clinical information. No overall association was observed between GSTM1 or GSTT1 null genotypes and colorectal cancer risk. However, the data suggest a possible role for GSTM1 genotype in influencing tumor site. Furthermore, GSTM1 and GSTT1 genotypes, in conjunction with gender and place of residence, may play a role in modifying disease risk. Further studies on a larger population in Egypt are needed to generalize the results of this study.

    View details for DOI 10.1016/S0304-3835(99)00159-7

    View details for Web of Science ID 000081180700014

    View details for PubMedID 10424787

  • Lung cancer after breast cancer: Does smoking or radiation therapy increase the risk of bronchoalveolar carcinoma? Stewart, E., Sigurdson, A., Ford, M., Ng, C., Cooksley, C., Kemp, B., McNeese, M., Spitz, M., Bondy, M. JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH. 1999: S70
  • Increased chromosomal instability in peripheral lymphocytes and risk of human gliomas CARCINOGENESIS El-Zein, R., Bondy, M. L., Wang, L. E., de Andrade, M., Sigurdson, A. J., Bruner, J. M., Kyritsis, A. P., Levin, V. A., Wei, Q. Y. 1999; 20 (5): 811–15

    Abstract

    Brain tumors exhibit considerable chromosome instability (CIN), suggesting that genetic susceptibility may contribute to brain tumorigenesis. To test this hypothesis, in this pilot study, we examined for CIN in short-term lymphocyte cultures from 25 adult glioma patients and 28 age-, sex- and ethnicity-matched healthy controls (all Caucasian). We evaluated CIN by a multicolor fluorescence in situ hybridization assay using two probes: a classic satellite probe for a large heterochromatin breakage-prone region of chromosome 1 and an alpha satellite probe for a smaller region adjacent to the heterochromatin probe. Our results showed a significant increase in the mean number of spontaneous breaks per 1000 cells in glioma patients (mean +/- SD, 2.4+/-0.8) compared with controls (1.4+/-0.9; P < 0.001). By using the median number of breaks per 1000 cells in the controls as the cutoff value, we observed a crude odds ratio (OR) of 8.5 [95% confidence interval (CI) = 2.05-34.9, P < 0.001] for spontaneous breaks and brain tumor risk. After adjustment for age, sex and smoking status, the adjusted OR was 15.3 (95% CI, 2.71-87.8). A significant increase in cells with chromosome 1 aneuploidy (in the form of hyperdiploidy) (P < 0.001) was also observed in the glioma cases, with an adjusted OR of 6.6 (95% CI = 1.5-30, P < 0.05). These findings suggest that CIN can be detected in the peripheral blood lymphocytes of brain tumor patients and may be a marker for identifying individuals at risk.

    View details for DOI 10.1093/carcin/20.5.811

    View details for Web of Science ID 000080022700010

    View details for PubMedID 10334198

  • Differential expression of MMAC/PTEN in glioblastoma multiforme: Relationship to localization and prognosis CANCER RESEARCH Sano, T., Lin, H., Chen, X. S., Langford, L. A., Koul, D., Bondy, M. L., Hess, K. R., Myers, J. N., Hong, Y. K., Yung, W. K., Steck, P. A. 1999; 59 (8): 1820–24

    Abstract

    MMAC/PTEN, a tumor suppressor gene located on chromosome 10q, has recently been shown to act as a phosphatidylinositol 3,4,5-triphosphate phosphatase and to modulate cell growth and apoptosis. Somatic mutations of MMAC/PTEN have been reported in a number of human cancers, especially in glioblastoma multiforme (GBM), although the number of identified mutations (approximately 10-35%) is significantly lower than the frequency of LOH affecting the MMAC/PTEN locus in the specimens (approximately 75-95%). To further investigate the possible alterations that may affect MMAC/PTEN, we examined the expression of the gene by reverse transcription-PCR in a series of gliomas. A significant difference (P < 0.001) was observed between the expression of MMAC/PTEN in GBMs versus lower grades of gliomas, thus mimicking the difference in allelic deletion associated with the locus in these tumors. Furthermore, Kaplan-Meier survival plots, adjusted for age and tumor grade, showed a significantly better prognosis for patients whose tumors expressed high levels of MMAC/PTEN. Additionally, immunostaining of GBMs revealed little or no MMAC/PTEN expression in about two-thirds of the tumors, whereas the other approximately one-third of tumors had significantly higher levels of expression. However, in about two-thirds of the high-expressing specimens, a heterogeneous pattern of expression was observed, indicating that certain cells within the tumor failed to express MMAC/PTEN. The combination of these results suggest that, in addition to molecular alterations affecting the gene, altered expression of MMAC/PTEN may play a significant role in the progression of GBM and patient outcome.

    View details for Web of Science ID 000079764900004

    View details for PubMedID 10213484

  • Three measures of mutagen sensitivity in a cancer-free population CANCER GENETICS AND CYTOGENETICS Gu, J., Bondy, M. L., Sigurdson, A., Spitz, M. R., Hsu, T. C., Wu, X. F. 1999; 110 (1): 65–69

    Abstract

    Different individuals appear to respond differently to the same carcinogen, and different mutagens act differently on cells. We conducted mutagen sensitivity assays by using three mutagens (bleomycin, a radiomimetic agent; 4-nitroquinoline-1-oxide [4-NQO], an ultraviolet light mimetic agent; and benzo[a]pyrene diol epoxide [BPDE], a tobacco mutagen) in parallel in healthy human subjects to determine the relationships among these assays. Our results showed that the mean breaks per cell values (b/c) (+/- SD) for bleomycin, 4-NQO, and BPDE sensitivity were 0.49 (+/- 0.26), 0.53 (+/- 0.30), and 0.66 (+/- 0.41), respectively. Age, sex, smoking status, and family history of cancer were not correlated with any of these mutagen sensitivities. Also, there was no correlation between bleomycin and 4-NQO or 4-NQO and BPDE sensitivity, but a weak correlation between bleomycin and BPDE was observed (correlation coefficient = 0.289; P = 0.001). When the 75th percentile of b/c was used as a cutoff point in each assay, only one individual (1.8%) was sensitive to all three mutagens. Ten individuals (17.9%) were sensitive to two mutagens, 20 (35.7%) to one mutagen, and 25 (44.6%) to none of three mutagens. Our study suggests that these three mutagens may involve different DNA damage and repair pathways. The lack of correlation between the assay results may indicate the necessity of using a battery of mutagen sensitivity tests to refine our ability to identify a subpopulation at high cancer risk.

    View details for DOI 10.1016/S0165-4608(98)00189-7

    View details for Web of Science ID 000079485600013

    View details for PubMedID 10198626

  • Colon cancer in young Egyptian patients AMERICAN JOURNAL OF GASTROENTEROLOGY Soliman, A. S., Bondy, M. L., Hamilton, Levin, B. 1999; 94 (4): 1114
  • The conditional probability of survival of patients with primary malignant brain tumors - Surveillance, epidemiology, and end results (SEER) data Davis, F. G., McCarthy, B. J., Freels, S., Kupelian, Bondy, M. L. WILEY-LISS. 1999: 485–91

    Abstract

    Five-year survival estimates in standard cancer reports provide a general description of disease outcome that is useful for surveillance and comparison purposes. However, for cancer survivors these overall survival rates may be discouraging, and the relevant question regarding an individual is this: Once he or she has survived for a specified period of time, what is the probability of survival over the next period of time?To address this, conditional survival rates by histology for malignant brain tumor survivors were estimated using the SEER public use data and the Portable Survival System, with 19,105 brain and other nervous system patients diagnosed between 1979 and 1993. Given that the survival curve declines more rapidly in the first 2 years than in subsequent years, conditional probabilities of surviving 5 years given survival to 2 years and 95% confidence intervals (CIs)were calculated. As age is a strong prognostic factor for these tumors, conditional probabilities were also estimated by categories of age.Estimated 2- and 5-year relative survival rates for patients with malignant brain and other CNS tumors were 36.2% and 27.6%; however, the conditional probability of surviving to 5 years, given survival to 2 years, reaches 76.2% (95% CI: 74.8-77.6). Conditional probabilities varied by histology and age at diagnosis. The conditional probability of surviving 5 years after surviving 2 years was 67.8% (95% CI: 62.6-73.1) for patients with anaplastic astrocytomas, 36.4% (95% CI: 31.9-41.6) for patients with glioblastomas, and 79.8% (95% CI:75.3-84.1) for patients with medulloblastomas.Conditional probabilities provide important and encouraging information for those who are brain tumor survivors. The utility of these estimates for other time intervals and other cancers or diseases should be considered.

    View details for DOI 10.1002/(SICI)1097-0142(19990115)85:2<485::AID-CNCR29>3.0.CO;2-L

    View details for Web of Science ID 000078208400029

    View details for PubMedID 10023719

  • A study of loss of heterozygosity at 70 loci in anaplastic astrocytoma and glioblastoma multiforme with implications for tumor evolution. Neuro-oncology Wooten, E. C., Fults, D., Duggirala, R., Williams, K., Kyritsis, A. P., Bondy, M. L., Levin, V. A., O'Connell, P. 1999; 1 (3): 169–76

    Abstract

    Cancers that arise from astrocytes in the adult CNS present as either anaplastic astrocytomas (AAs) or as more aggressive glioblastomas multiforme (GBMs). GBMs either form de novo or progress from AAs. We proposed to examine the molecular genetic relationship between these CNS tumors by conducting a genome-wide allelic imbalance analysis that included 70 loci on examples of AA and GBM. We found significant loss of heterozygosity (LOH) at 13 discrete chromosomal loci in both AAs and GBMs. Loss was significant in both AAs and GBMs at 9 of these loci. AAs show the highest rates of LOH at chromosomes 1p, 4q, 6p, 9p, 11p, 11q, 13q, 14q, 15p, 17p, 17q, and 19q. GBMs showed the greatest losses at 1p, 6q, 8p, 9p, 10p, 10q, 11p, 13q, 17p, 17q, 18p, 18q, and 19q. GBMs also demonstrated significant amplification at the epidermal growth factor receptor locus (7p12). These data suggest that there are three classes of loci involved in glioma evolution. First are loci that are likely involved in early events in the evolution of both AAs and GBMs. The second class consists of AA-specific loci, typified by higher LOH frequency than observed in GBMs (4q, 6p, 17p, 17q, 19q). The third class consists of GBM-specific loci (6q, 8p, 10, 18q). Damage at these loci may either lead to de novo GBMs or permit existing AAs to progress to GBMs. Glioma-related LOH profiles may have prognostic implications that could lead to better diagnosis and treatment of brain cancer patients.

    View details for DOI 10.1093/neuonc/1.3.169

    View details for PubMedID 11550311

  • gamma-ray mutagen sensitivity and survival in patients with glioma CLINICAL CANCER RESEARCH Sigurdson, A. J., Bondy, M. L., Hess, K. R., Toms, S. A., Kyritsis, A. P., Gu, J., Wang, L. E., Wang, X. Z., Adatto, P., Bruner, J. L., Yung, W. K., Levin, V. A., Wei, Q. Y. 1998; 4 (12): 3031–35

    Abstract

    Despite advances in treatment of brain tumors, cerebral malignant gliomas are rapidly debilitating with poor survival. Patient age and tumor histology are known to influence survival in glioma patients, but these factors do not account for all of the variability in survival time. To identify additional useful predictors, we tested an assay that measures intrinsic gamma-ray mutagen sensitivity. Our hypothesis was that increased sensitivity of peripheral blood lymphocytes to chromatid breaks is associated with tumor aggressiveness and decreased patient survival. The eligible 76 patients were those with histologically confirmed malignant gliomas, seen at the University of Texas M. D. Anderson Cancer Center between 1994 and 1997, for whom we had sufficient blood for the in vitro gamma-radiation assay. After gamma-irradiation of each subject's lymphocytes, the frank chromatid breaks in 50 metaphases were averaged to calculate breaks/cell. On the basis of our patient series, we established a gamma-ray mutagen sensitivity cutoff point of 0.55 breaks/cell that was confirmed by bootstrap resampling techniques. Patients with values >0.55 breaks/cell were considered sensitive. Kaplan-Meier and Cox proportional hazards modeling were used for the analysis. The gamma-ray mutagen-sensitive patients had worse survival than the nonsensitive patients, with an unadjusted hazard rate ratio of 1.6 (95% confidence interval, 0.9-2.8; P = 0.15). After adjustment for age, tumor histology, and extent of surgical resection, the hazard rate ratio was 2.4 (95% confidence interval, 1.3-4.6; P = 0.0081). Our data suggest that gamma-ray mutagen sensitivity is a prognostic indicator of survival in glioma patients. The significance of these findings needs to be verified in studies with larger samples of patients with histologically similar gliomas.

    View details for Web of Science ID 000077423700016

    View details for PubMedID 9865917

  • Allelic deletion analyses of MMAC/PTEN and DMBT1 loci in gliomas: Relationship to prognostic significance CLINICAL CANCER RESEARCH Lin, H., Bondy, N. L., Langford, L. A., Hess, K. R., Delclos, G. L., Wu, X. F., Chan, W. Y., Pershouse, M. A., Yung, W. K., Steck, P. A. 1998; 4 (10): 2447–54

    Abstract

    The frequency of loss of heterozygosity (LOH) around MMAC/PTEN and DMBT1 loci and survival analyses based on the LOH status were assessed in 110 patients with different histological groups of gliomas. Twenty-six of the patients had anaplastic oligodendrogliomas, 31 had anaplastic astrocytomas, and 53 had glioblastomas multiforme (GM). At the DMBT1 locus, LOH was observed very frequently in all three histological groups, with no significant difference in the frequency of LOH among the three histological groups. At the MMAC/PTEN locus, patients with GM exhibited a significantly increased frequency of LOH (72%) compared with patients with anaplastic astrocytomas (29%) or anaplastic oligodendrogliomas (31%) (P < 0.0001). Kaplan-Meier survival plots showed that patients with LOH at the MMAC/PTEN locus had a significantly worse prognosis than did patients without LOH at the MMAC/PTEN locus [hazard ratio (LOH versus non-LOH), 2.65; 95% confidence interval (CI), 1.69-4.46; P < 0.0001]. Cox proportional hazards regression analysis, adjusted for age at surgery and histological grades (GM and non-GM), showed that LOH at the MMAC/PTEN locus was a significant predictor of shorter survival [hazard ratio (LOH versus non-LOH), 2.01; 95% CI, 1.1-3.5; P = 0.018). Our analysis failed to indicate a similar association between the frequency of LOH at the DMBT1 locus and patient survival [hazard ratio (LOH versus non-LOH), 2; 95% CI, 0.37-3.13; P = 0.2]. These results suggest that the DMBT1 gene may be involved early in the oncogenesis of gliomas, whereas alterations in the MMAC/PTEN gene may be a late event in the oncogenesis related to progression of gliomas and provide a significant prognostic marker for patient survival.

    View details for Web of Science ID 000076366700021

    View details for PubMedID 9796977

  • Familial aggregation of colorectal cancer in Egypt INTERNATIONAL JOURNAL OF CANCER Soliman, A. S., Bondy, M. L., Levin, B., El-Badawy, S., Khaled, H., Hablas, A., Ismail, S., Adly, M., Mahgoub, K. G., McPherson, R. S., Beasley, R. P. 1998; 77 (6): 811–16

    Abstract

    We have investigated the familial aggregation of colorectal cancer and hereditary nonpolyposis colorectal cancer (HNPCC) in Egypt because of the high incidence of colorectal cancer in Egyptian children and young adults and the prevalence of consanguinity there. In a pilot study, we conducted detailed interviews with 111 Egyptian colorectal cancer patients and 111 healthy Egyptian controls about their family histories of colorectal cancer, and other cancers, consanguinity, age at diagnosis, symptoms and recurrence. Eight patients (7.2%) had one or more first- or second-degree relatives under age 40 with colorectal cancer, suggestive of HNPCC by the Amsterdam criteria. One of these families had a typical history of HNPCC, with 4 relatives having colorectal cancer in 3 generations; 3 of these relatives were younger than age 45 at colon cancer diagnosis, and other relatives had extracolonic tumors. Another 14 patients (12.6%) had a first- or second-degree relative with a family history of other neoplasms such as endometrial, urinary and hepatobiliary cancers that could also be related to HNPCC. Four patients with early-onset colon cancer and a family history of other HNPCC-related cancers reported that their parents were first-degree cousins.

    View details for DOI 10.1002/(SICI)1097-0215(19980911)77:6<811::AID-IJC1>3.0.CO;2-X

    View details for Web of Science ID 000075401400001

    View details for PubMedID 9714045

  • Genetic polymorphisms in glutathione S-transferase mu and theta, N-acetyltransferase, and CYP1A1 and risk of gliomas CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Trizna, Z., de Andrade, M., Kyritsis, A. P., Briggs, K., Levin, V. A., Bruner, J. M., Wei, Q. Y., Bondy, M. L. 1998; 7 (6): 553–55

    Abstract

    The role of genetic polymorphisms in modulating susceptibility to carcinogenic exposures has been well explored for tobacco-related neoplasms but not for other neoplasms including gliomas. It is relevant to explore these polymorphisms because certain carcinogenic exposures such as nitrosamines are implicated in the risk of gliomas. We therefore conducted a pilot case-control study to examine the role of polymorphisms in GSTM1, GSTT1, NAT2 (rapid, intermediate, and slow acetylation), and CYP1A1 and risk of glioma. Ninety patients diagnosed with glioma were ascertained as part of an ongoing genetic epidemiological study and were age, gender, and race matched with 90 healthy controls. We used PCR based methodology to determine the prevalence of the above genetic polymorphisms using sequences and PCR conditions directly adapted from studies reported previously. We calculated univariate odds ratios and performed multiple logistic regression to assess interactions between polymorphisms. We found no statistically significant associations between the null genotypes of GSTM1 and GSTT1, and CYP1A1 and risk of gliomas. However, there was an intriguing pattern with NAT2 acetylation status (odds ratios, 1.81, 1.34, and 0.61 for rapid, intermediate, and slow acetylation, respectively; P = 0.10 for trend). It is unlikely that any single polymorphism is sufficiently predictive of risk, and a panel of markers integrated with epidemiological data should be conducted on a large number of study subjects to fully understand the role of genetic polymorphisms and brain tumor risk.

    View details for Web of Science ID 000074029000016

    View details for PubMedID 9641501

  • Reduced expression of mismatch repair genes in colorectal cancer patients in Egypt INTERNATIONAL JOURNAL OF ONCOLOGY Soliman, A. S., Bondy, M. L., Guan, Y., El-Badawi, S., Mokhtar, N., Bayomi, S., Raouf, A. A., Ismail, S., McPherson, R. S., Abdel-Hakim, T. F., Beasley, R. P., Levin, B., Wei, Q. Y. 1998; 12 (6): 1315–19

    Abstract

    An Egyptian hospital-based pilot case-control study was conducted to investigate the relationship between the expression level of mismatch repair (MMR) genes and the risk of colorectal cancer. The relative expression of five known MMR genes, i.e., hMSH2, hMLH1, hPMS1, hPMS2, and GTBP/hMSH6, was measured by a multiplex reverse transcriptase (RT)-polymerase chain reaction (PCR) in peripheral blood lymphocytes from 31 colorectal cancer patients and 47 age- and-sex matched controls. The expression of hMSH2, GTBP/hMSH6, hPMS1 and hPMS2 tended to be lower in patients than controls, but only the difference in hPMS2 expression was statistically significant (p<0. 01). Although 50% of the cases had chemotherapy or radiotherapy within the last six months before the blood was drawn, their gene expression was not statistically different from those who had not undergone such therapies. After adjustment for age and sex, the odds ratios (OR) calculated from a logistical regression model, using the median levels of gene expression of controls as cut-off values, indicated that increased risk was associated with reduced expressions of both hPMS1 (OR = 3.97, 95% confidence interval (CI) = 1.04 to 7.65) and hPMS2 (OR = 2.86, 95% CI = 1.05 to 7.76). Although the results of this study were inconclusive because of the small sample size and use of prevalent cases, it is biologically plausible that patients with colorectal cancers may have a lower expression of MMR genes than healthy controls because malfunction of these genes has been shown in hereditary nonpolyposis colon cancer. The involvement of low hPMS2 expression in colon cancer risk seems to be unique in the Egyptian population. Further studies with newly diagnosed patients before they begin therapy will provide more convincing data about the role of MMR gene expression in the etiology of colorectal cancers in Egypt.

    View details for Web of Science ID 000073815500016

    View details for PubMedID 9592192

  • The molecular pathology of colorectal cancer in patients under the age of 40 years in Egypt. Soliman, A. S., Levin, B., Bondy, M. L., Eissa, S., Mokhtar, N., El-Badawi, S., Bayomi, S., Ismail, K., Watanabe, T., Longi, P., Houlihan, S., Hamilton W B SAUNDERS CO. 1998: A682
  • Family history of cancer in patients with glioma: A validation study of accuracy JOURNAL OF THE NATIONAL CANCER INSTITUTE Airewele, G., Adatto, P., Cuningham, J., Mastromarino, C., Spencer, C., Sharp, M., Sigurdson, A., Bondy, M. 1998; 90 (7): 543–44

    View details for DOI 10.1093/jnci/90.7.543

    View details for Web of Science ID 000072776500015

    View details for PubMedID 9539252

  • Prostate-specific antigen levels are higher in African-American than in white patients in a multicenter registration study: Results of RTOG 94-12 INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Vijayakumar, S., Winter, K., Sause, W., Gallagher, M. J., Michalski, J., Roach, M., Porter, A., Bondy, M. 1998; 40 (1): 17–25

    Abstract

    To compare serum prostate-specific antigen (PSA) levels in a national sample of African-American and white men with prostate cancer, and to attempt to explain any differences by using self-reported individual-level socioeconomic status adjustments.During 4 1/2 months in 1994-95, 709 patients with nonmetastatic prostate cancer were enrolled in this prospective study; 17.5% were African-American and 82.5% were white. Information about clinical stage, tumor grade, pretreatment PSA, type of insurance, and educational and income status was obtained. Serum PSA levels were measured and racial differences were found; how the differences were influenced by other patient- or tumor-related factors and if the differences could be explained by socioeconomic status disparities were determined. In univariate analyses, factors associated with the mean PSA levels were studied; log-converted values were used to yield a normal distribution. Multivariate analyses were done on log-linear models for description of association patterns among various categorical variables; a perfectly fitted model should have a correlation value (CV) of 1.0.The mean PSA level was higher in African-Americans (14.68 ng/ml) than in whites (9.82 ng/ml) (p = 0.001). Clinical stage (p = 0.001), Gleason sum tumor grade (p = 0.0001), educational level (p = 0.001), and household income (p = 0.03) were also associated with mean PSA levels; age, type of biopsy, and insurance status were not. Disease stage (p = 0.0001), grade (p = 0.0001), education (p = 0.07), and income (p = 0.02) were all associated with PSA levels for whites, but none of these factors were important for African-Americans (all p values > 0.1). The best fitted log-linear model (CV = 0.99) contained PSA (< 10, 10-20, and > 20), Gleason sum grade (2-5, 6-7, and 8-10), race, and two interactions: PSA by race (p = 0.0012) and PSA by Gleason sum (p = 0.0001). Models replacing race for either income (CV = 0.82) or education (CV = 0.82) or both (CV = 0.78) did not fit as well.African-Americans with nonmetastatic prostate cancer have higher serum PSA levels at diagnosis than whites, implying a higher tumor cell burden. Individual-level household income, education, or insurance status alone or in combination account for racial differences, but only partially.

    View details for DOI 10.1016/S0360-3016(97)00834-1

    View details for Web of Science ID 000071164200005

    View details for PubMedID 9422553

  • Clinicopathologic features of bilateral breast cancer. Sahin, A., Cunningham, J., Bondy, M., Aldaz, C. LIPPINCOTT WILLIAMS & WILKINS. 1998: 26A
  • Clinicopathologic features of bilateral breast cancer. Sahin, A., Cunningham, J., Bondy, M., Aldaz, C. LIPPINCOTT WILLIAMS & WILKINS. 1998: 26A
  • Sociodemographic analysis of patients in radiation therapy oncology group clinical trials INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Chamberlain, R. M., Winter, K. A., Vijayakumar, S., Porter, A. T., Roach, M., Streeter, O., Cox, J. D., Bondy, M. L. 1998; 40 (1): 9–15

    Abstract

    To assess the degree to which the sociodemographic characteristics of patients enrolled in Radiation Therapy Oncology Group (RTOG) clinical trails are representative of the general population.Sociodemographic data were collected on 4016 patients entered in 33 open RTOG studies between July 1991 and June 1994. The data analyzed included educational attainment, age, gender, and race. For comparison, we obtained similar data from the U.S. Department of Census. We also compared our RTOG data with Surveillance Epidemiology and End Results (SEER) data for patients who received radiation therapy, to determine how RTOG patients compared with cancer patients in general, and with patients with cancers at sites typically treated with radiotherapy.Overall, the sociodemographic characteristics of patients entered in RTOG trials were similar to those of the Census data. We found that, in every age group of African-American men and at nearly every level of educational attainment, the proportion of RTOG trial participants mirrored the proportion in the census data. Significant differences were noted only in the youngest category of African-American men, where the RTOG accrues more in the lower educational categories and fewer with college experience. For African-American women, we found a similar pattern in every age group and at each level of educational attainment. As with men, RTOG trials accrued a considerably larger proportion of younger, less educated African-American women than the census reported. Using SEER for comparison, the RTOG enrolled proportionately more African-American men to trials all cancer sites combined, and for prostate and head and neck cancer. In head and neck trials, the RTOG enrolled nearly twice as many African-American men than would be predicted by SEER data. In lung cancer trials, RTOG underrepresented African-American men significantly; however, there was no difference for brain cancer trials. There were no racial differences in RTOG accrual and SEER incidence data for women on trials in brain, lung, and head and neck cancer. However, the RTOG trials accrued nearly twice the proportion of African-American women in cervical cancer trials and in all sites combined, compared to the SEER data.Comparisons with the U.S. Census and SEER show that African-Americans are proportionally well represented in cancer clinical trials conducted by the Radiation Therapy Oncology Group. The comparative analysis indicates that all educational levels in each age group of African-Americans generally mirror the U.S. Census, with one exception. The exception is a significant overrepresentation of less-educated African-Americans in the youngest age category. This exception is counter to the expectation that better-educated patients are more likely to enroll in trials. When compared with SEER data, the RTOG trials either parallel or overrepresent African-American men and women, with the only exception being in lung cancer, where men are underrepresented. These results show that, in comparison to the Census and SEER data, the RTOG has fulfilled its commitment to enroll African-American patients in its clinical trials.

    View details for DOI 10.1016/S0360-3016(97)00833-X

    View details for Web of Science ID 000071164200004

    View details for PubMedID 9422552

  • Serum organochlorine pesticide levels in patients with colorectal cancer in Egypt ARCHIVES OF ENVIRONMENTAL HEALTH Soliman, A. S., Smith, M. A., Cooper, S. P., Ismail, K., Khaled, H., Ismail, S., McPherson, R. S., Seifeldin, I. A., Bondy, M. L. 1997; 52 (6): 409–15

    Abstract

    The widespread use of pesticides in Egypt, the high incidence of colorectal cancer in Egyptian children and young adults, and the published U.S. case reports in which pesticides have been connected with colorectal cancer led the authors to investigate the possible association between organochlorines and colorectal cancer. The authors conducted a pilot study to describe serum organochlorine levels among 31 Egyptian colorectal patients and 17 controls. High levels and large interindividual variability of p,p'-dichloro-diphenyldicholoroethylene (DDE), dichloro-diphenyl-trichloroanthane (DDT), beta-hexachlorocyclohexane (beta-HCH), and hexachlorobenzene (HCB) levels were found among most subjects, especially those from rural areas. Farming and aging were each associated positively with high serum organochlorines. Colorectal cancer patients had higher serum organochlorines levels than controls. The high levels of organochlorines reported and their relation to age, residence, occupation, and disease status justify further study of the possible association between organochlorine pesticides and colorectal cancer in a larger population in Egypt.

    View details for DOI 10.1080/00039899709602219

    View details for Web of Science ID 000072877500002

    View details for PubMedID 9541361

  • Ethical issues of genetic testing and their implications in epidemiologic studies Bondy, M., Mastromarino, C. ELSEVIER SCIENCE INC. 1997: 363–66

    Abstract

    To discuss and summarize the ethical controversies related to genetic testing and screening, and their effects on the research and other professional activities of epidemiologists.We reviewed the literature and proposed legislation to discuss the controversies related to the ethical issues of genetic testing in epidemiologic research.From a review of the literature and proposed legislation, we found these controversies may continue for some time and will probably add to the duties and difficulties of epidemiologists. It is important for the profession to respond to developments such as the proposed federal Genetic Confidentiality and Nondiscrimination Act of 1996 (Senate Bill 1898), which is summarized here; changes in research protocols and informed-consent forms as well as inclusion of other professionals from many disciplines will be necessary. In addition to revising training, and expanding their ethical code, epidemiologists should respond to public concerns about genetic information by disseminating knowledge about freedom to conduct clinical research, protection of the individual, and the limits of genetic information.The possibility of genetic discrimination may complicate epidemiological research unless the public, employers, insurers, physicians, and researchers reach a consensus on the meaning of, and need for, genetic information. Although ethical concerns are appropriate, they will make accrual of study subjects and tissue samples more difficult.

    View details for DOI 10.1016/S1047-2797(97)00029-X

    View details for Web of Science ID A1997XN53300008

    View details for PubMedID 9250632

  • Reduced expression of mismatch repair genes measured by multiplex reverse transcription polymerase chain reaction in human gliomas CANCER RESEARCH Wei, Q. Y., Bondy, M. L., Mao, L., Guan, Y. L., Cheng, L., Cunningham, J., Fan, Y. H., Bruner, J. M., Yung, W. K., Levin, V. A., Kyritsis, A. P. 1997; 57 (9): 1673–77

    Abstract

    Microsatellite instability (MIN) is frequently observed in hereditary nonpolyposis colon cancer and in other sporadic cancers including gliomas. Abnormalities in at least one of five mismatch repair (MMR) genes are implicated in the development of cancers in hereditary nonpolyposis colon cancer and the associated MIN. Using a newly developed multiplex reverse transcription-PCR assay, we evaluated the expression of the five known human MMR genes (hMSH2, hMLH1, hPMS1, hPMS2, and GTBP) in human gliomas by measuring simultaneously the relative levels of the transcripts. The beta-actin gene was used as an internal control for RNA degradation and DNA contamination and as a reference for quantifying the levels of their transcripts. Of the 33 gliomas examined, 42% (14) had low expression of hMSH2 (at least 4-5-fold lower than normal mean), 21% (7) had low expression of hMLH1, and 18% (6) had low expression of hPMS1 compared with the expression in the lymphocytes from 13 normal individuals. Furthermore, six of the 33 (18%) tumor samples had decreased expression of more than one MMR gene. Two of these six patients with multiple gene abnormalities had second primary cancers, and an additional patient had multifocal gliomas. Further molecular analysis of available DNA samples indicated that one of five of those tumors with aberrant expression of MMR genes had MIN, as compared with none of five tumors with normal expression. These data suggest that reduced expression of MMR genes is frequent in human gliomas and that aberrant expression of more than one MMR gene may be associated with increased risk of second primary malignancies in glioma patients.

    View details for Web of Science ID A1997WW56900012

    View details for PubMedID 9135006

  • Colorectal cancer in young Egyptians under the age of 40. Soliman, A. S., Bondy, M. L., McPherson, R. S., Hamza, M. R., Ismail, M. D., Ismail, S. E., Hammam, H. M., Levin, B., Beasley, P. W B SAUNDERS CO-ELSEVIER INC. 1997: A659
  • Colorectal cancer in Egyptian patients under 40 years of age INTERNATIONAL JOURNAL OF CANCER Soliman, A. S., Bondy, M. L., Levin, B., Hamza, M. R., Ismail, K., Ismail, S., Hammam, H. M., ElHattab, O. H., Kamal, S. M., Soliman, A. G., Dorgham, L. A., McPherson, R. S., Beasley, R. P. 1997; 71 (1): 26–30

    Abstract

    Although colorectal cancer is not a common cancer in Egypt, the age distribution of the disease shows that a high proportion occurs in children and adults under 40 years of age. We reviewed the records of 1,608 colorectal cancer patients treated in 4 cancer hospitals in Egypt during a period of 3 to 10 years. The hospitals in which about 85% of all colorectal cancer cases in Egypt were seen included Egypt's 2 major cancer centers, The National Cancer Institute (NCI) in Cairo and Tanta Cancer Center (TCC) in the mid-Nile Delta region, and 2 major university hospitals, Assiut University in South Egypt and Ain Shams University in Cairo. Our review showed that patients younger than 40 years represented 35.6% of all patients in the 4 cancer hospitals, and that these rates were similar among the hospitals and for the years reviewed. The male-to-female ratio increased from 1.0 to 1.7 for the age groups ranging from 0-9 and 30-39 years, and increased from 1.0 to 1.5 for the age groups ranging from 40-49 to over 60 years. More than half of all the patients had rectal tumors, and about 90% of the cancers were adenocarcinomas; 30.6% of patients younger than 40 years, compared with 13.8% of older patients, had mucin-producing tumors. This study confirmed the occurrence of a high colorectal cancer rate in young Egyptians, and it opens the door to future epidemiologic studies to identify causes and risk factors of this disease pattern in Egypt.

    View details for DOI 10.1002/(SICI)1097-0215(19970328)71:1<26::AID-IJC6>3.0.CO;2-5

    View details for Web of Science ID A1997WQ88400006

    View details for PubMedID 9096661

  • Benzo(a)pyrene diol epoxide-induced chromosomal aberrations and risk of lung cancer CANCER RESEARCH Wei, Q. Y., Gu, J., Cheng, L., Bondy, M. L., Jiang, H., Hong, W. K., Spitz, M. R. 1996; 56 (17): 3975–79

    Abstract

    Benzo(a)pyrene is considered a classic DNA-damaging carcinogen and is one of a multitude of polycyclic aromatic hydrocarbons commonly found in tobacco smoke and in the ambient environment. In this report, we describe the characteristics of chromosomal aberrations induced in vitro by activated benzo(a)pyrene diol epoxide (BPDE) in lymphocyte cultures of 172 normal individuals ages 19-95 years and present the analysis of a pilot case-control study of 33 lung cancer patients and 96 selected controls without history of cancer and frequency matched on age (50-85 years) to the cases. The BPDE-induced chromosomal aberrations were predominantly single chromatid breaks, with few isochromatid breaks or exchange figures. In the 172 normal subjects, the frequencies of both spontaneous and BPDE-induced chromatid breaks were not correlated with age, sex, ethnicity, or tobacco use. However, the frequency of BPDE-induced chromatid breaks was significantly correlated with the frequency of spontaneous chromatid breaks (r = 0.19, P < 0.05). In addition, Hispanics had significantly higher mean BPDE-induced chromatid breaks than did non-Hispanic whites (P < 0.01). From the case-control analyses, the frequency of BPDE-induced chromosomal aberrations was significantly higher in cases (mean, 0.67 breaks/cell) than in controls (mean, 0.41 breaks/cell; P < 0.0001). An adjusted odds ratio of 6.53 (95% confidence interval, 3.74-11.4) for lung cancer was associated with increased frequency of these chromosomal aberrations. The higher rate of BPDE-induced chromosomal aberrations may be due to inefficient DNA repair. These findings warrant additional molecular epidemiological studies. The BPDE mutagen sensitivity assay will facilitate epidemiological studies of genetic susceptibility to smoking-related cancers.

    View details for Web of Science ID A1996VE08300024

    View details for PubMedID 8752166

  • Epidemiology and etiology of intracranial meningiomas: A review Bondy, M., Ligon, B. L. KLUWER ACADEMIC PUBL. 1996: 197–205

    Abstract

    The frequency of meningiomas has been the topic of relatively few reports. Hospital-based brain tumor series indicate that the incidence is approximately 20% of all intracranial tumors; population-based studies indicate an overall incidence of 2.3/100,000. Although intracranial tumors as a whole show a higher prevalence in males than in females, meningiomas have a 2:1 female-to-male ratio. Between Caucasians and Africans, African-Americans, and Asians, certain differences also have been noted. Meningiomas in children are rare and differ from those in adults and other childhood tumors; they are even more rare in infants. Several features indicating etiologic factors have been identified, among which are ionizing radiation, head injury, hormones, and other receptor binding sites, genetic factors, and viruses. The most common source of exposure of the head to ionizing radiation is dental radiographic examination. Since 1922, head trauma has been considered a possible risk factor, but recent large studies do not support this link. Several factors have prompted studies of estrogens and progestogens as risk factors for meningiomas. Other studies have sought to determine if certain individuals have an inherited predisposition for developing a meningioma and/or if viruses, which may act alone or with other mutagens, figure into the formation of a meningioma. The most promising studies are those of cytogenetics, and future elucidation of factors associated with the loss of one copy of chromosome 22, another phenomenon that has been identified in meningiomas, may lead to screening tests and gene therapy.

    View details for DOI 10.1007/BF00165649

    View details for Web of Science ID A1996VB11900002

    View details for PubMedID 8858525

  • Mutagen sensitivity and risk of gliomas: A case-control analysis CANCER RESEARCH Bondy, M. L., Kyritsis, A. P., Gu, J., deAndrade, M., Cunningham, J., Levin, V. A., Bruner, J. M., Wei, Q. Y. 1996; 56 (7): 1484–86

    Abstract

    Although the risk factors contributing to the etiology of brain tumors remain largely unknown, this pilot study suggests that genetically determined sensitivity to environmental carcinogens may play a role in the pathogenesis of these tumors. In this study, we examined short-term lymphocyte cultures from 45 adult malignant glioma patients and 117 age-, sex-, and ethnicity-matched healthy controls for mutagen-induced chromatid breaks and evaluated their family history of cancer, smoking, and demographic variables to ascertain the association between mutagen sensitivity and risk of brain tumors. The mutagen selected was gamma-radiation. The mean number of induced breaks/cell was 0.72 (SD=0.45) for the cases and 0.45 (SD = 0.35) for the controls (P < 0.0001). Using the median number of induced breaks/cell in the controls as the breakpoint for defining mutagen sensitivity, we observed an unadjusted odds ratio of 5.36 (95% confidence interval = 2.12-13.69) for mutagen sensitivity and brain tumor risk and an adjusted odds ratio of 5.79 (2.26-14.83), when we controlled for epidemiological risk factors including smoking, race, income, and education. Although a larger study is needed to confirm this intriguing result, these preliminary findings suggest that increased sensitivity to radiation is an independent risk factor for gliomas.

    View details for Web of Science ID A1996UC16700005

    View details for PubMedID 8603389

  • Mutations of the p16 gene in gliomas ONCOGENE Kyritsis, A. P., Zhang, B. H., Zhang, W., Xiao, M., Takeshima, H., Bondy, M. L., Cunningham, J. E., Levin, V. A., Bruner, J. 1996; 12 (1): 63–67

    Abstract

    In the present study we investigated the frequency of p16 gene exon 2 mutations in 35 malignant gliomas, using either direct sequencing of the PCR products or cloning into the pCRII vector and sequencing of the cloned PCR products. No mutations were detected during direct sequencing of the PCR products. However, after sequencing of individual clones, we found multiple mutations in 5 tumors involving codons 73(GCC to ACC, Ala to Thr), 76 (GCC to GTC, Ala to Val), 85(GCT to ACT, Ala to Thr), 98(CAC to TAC, His to Tyr), 102 (GCG to GTG, Ala to Val), 106 (GTG to ATG, Val to Met), 107 (CGC to TGC, Arg to Cys), 127 (GCA to GTA, Ala to Val), 128 (CGG to TGG, Arg to Trp) and 136 (GGC to GAC, Gly to Asp). Mutations were found only in glioblastomas and were either C to T or G to A transitions. Each mutation was detected in a small percentage of tumor cells (1.3-22%) using individual colony sequencing and southern hybridization with mutant oligonucleotides, consistent with the heterogenous cell population of glioblastomas. The presence of p16 gene mutations only in glioblastomas suggests that they are late events in glioma development.

    View details for Web of Science ID A1996TQ01400008

    View details for PubMedID 8552400

  • Correlation of p53 immunoreactivity and sequencing in patients with glioma MOLECULAR CARCINOGENESIS Kyritsis, A. P., Xu, R. S., Bondy, M. L., Levin, V. A., Bruner, J. M. 1996; 15 (1): 1–4

    Abstract

    This study examines the relationship between p53 immunostaining and direct sequencing of polymerase chain reaction (PCR) products in 61 gliomas. Glioma tissues obtained from patients at surgery were analyzed immunohistochemically with the monoclonal antibody PAb1801 to detect p53 protein abnormalities. Amplified p53 cDNA from these samples was analyzed by direct sequencing. Four grades of p53 immunostaining were evaluated: grade 0 = no labeling, grade 1 = less than 5% labeled cells, grade 2 = 5-30% labeled cells, and grade 3 = more than 30% labeled cells. Twenty-six of 36 glioblastomas, 14 of 23 anaplastic gliomas, and none of two low-grade gliomas had positive p53 immunoreactivity. Direct sequencing of PCR-amplified p53 cDNA revealed that 10 glioblastomas, 11 anaplastic gliomas, and no low-grade gliomas had mutations. Comparison of p53 immunostaining and sequencing data revealed that among all the gliomas, mutations were found in three of 21 with p53 grade 0, one of 16 with p53 grade 1, seven of nine with p53 grade 2, and 10 of 15 with p53 grade 3. These results indicate a good correlation between the p53 immunostaining and sequencing data when the percentage of abnormal cells within the tumor was greater than 5% (p53 grades 2 and 3). However, the correlation was poor when the percentage of abnormal cells was less than 5% (p53 grade 1) because of the limited sensitivity of sequencing techniques. Thus, p53 immunostaining may be more accurate in detecting p53 alterations when the percentage of abnormal cells is small; however, in rare cases, p53 immunostaining may fail to detect mutations confirmed by sequencing.

    View details for Web of Science ID A1996TR17600001

    View details for PubMedID 8561860

  • Prognostic significance of p53 immunoreactivity in patients with glioma CLINICAL CANCER RESEARCH Kyritsis, A. P., Bondy, M. L., Hess, K. R., Cunningham, J. E., Zhu, D., Amos, C. J., Yung, W. K., Levin, V. A., Bruner, J. M. 1995; 1 (12): 1617–22

    Abstract

    Abnormal p53 as revealed by immunostaining has been shown to be a predictor of poor outcome in a variety of malignant tumors. This study examines the relationship of p53 immunostaining and survival in 182 adult patients with gliomas. Tumor tissues obtained from patients with glioma within 4 months of initial diagnosis were investigated by immunohistochemical analysis for detection of p53 protein abnormalities using the monoclonal antibody PAb 1801. There were 122 patients with glioblastoma multiforme, 48 patients with anaplastic glioma, and 12 patients with low-grade glioma. Among these patients, 73 of those with glioblastoma multiforme, 35 with anaplastic glioma, and 6 with low-grade glioma had positive p53 immunoreactivity. Kaplan-Meier survival plots (log rank test) showed that the patients with anaplastic astrocytoma or low-grade glioma and p53-positive tumors had longer survival times compared to the patients with p53-negative tumors. No differences in survival were detected among the glioblastoma patients. Cox proportional hazards regression analysis, adjusted for age at diagnosis, showed that the p53 positivity was a significant predictor of longer survival (relative risk = 0.56; 95% confidence intervals = 0.35, 0.90; P = 0. 015) in anaplastic astrocytoma patients, but not in glioblastoma patients (relative risk = 1.03; 95% confidence intervals = 0.82, 1. 29; P = 0.80). These results suggest that anaplastic glioma patients with p53 protein alterations may have a better response to chemoradiation, possibly because the malignant cells cannot arrest in G1 to correct lethal damage induced by chemotherapy or radiotherapy.

    View details for Web of Science ID A1995TL02000023

    View details for PubMedID 9815964

  • COMPARATIVE ALLELOTYPE OF IN-SITU AND INVASIVE HUMAN BREAST-CANCER - HIGH-FREQUENCY OF MICROSATELLITE INSTABILITY IN LOBULAR BREAST CARCINOMAS CANCER RESEARCH ALDAZ, C. M., CHEN, T. P., SAHIN, A., CUNNINGHAM, J., BONDY, M. 1995; 55 (18): 3976–81

    Abstract

    To better understand the timing for presentation of allelic losses in human breast carcinogenesis, we compared the allelotypic profile of 23 in situ ductal carcinomas with that of 29 invasive ductal carcinomas. We also compared the allelotype of the invasive ductal breast carcinomas with that of 23 invasive lobular breast carcinomas. These studies were performed by means of microsatellite length polymorphisms from microdissected paraffin sections. We observed that involvement of chromosome arms 1p, 3p, 3q, 6p, 16p, 18p, 18q, 22q, and possibly 6q and 11p appear to be late events in breast cancer progression because allelic losses or imbalances affecting these areas were observed with very low frequency at the in situ stage. On the other hand, allelic imbalances and losses affecting chromosome arms 7p, 16q, 17p, and 17q appear to be early abnormalities because they were observed in approximately 25-30% of ductal carcinoma in situ lesions. Allelic losses and imbalances affecting the 8p arm were frequently observed in invasive lobular breast carcinomas. It was also interesting that microsatellite instability, also known as replication error (RER) phenotype, was found to occur at a high frequency in invasive lobular breast carcinomas because 9 of 23 (39%) were RER+, compared with 7 of 52 (13.5%) RER+ of breast cancers with ductal differentiation (P = 0.012, chi 2 test). Our findings provide for the first time molecular evidence suggesting that invasive lobular breast carcinomas may arise by a different mechanism of carcinogenesis than ductal carcinomas.

    View details for Web of Science ID A1995RV09900008

    View details for PubMedID 7664266

  • A CASE-CONTROL STUDY OF WOOD DUST EXPOSURE, MUTAGEN SENSITIVITY, AND LUNG-CANCER RISK CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION WU, X. F., DELCLOS, G. L., ANNEGERS, J. F., BONDY, M. L., HONN, S. E., HENRY, B., HSU, T. C., SPITZ, M. R. 1995; 4 (6): 583–88

    Abstract

    The associations between lung cancer risk, mutagen sensitivity (a marker of cancer susceptibility), and a putative lung carcinogen, wood dust, were assessed in a hospital-based case-control study. There were 113 African -American and 67 Mexican-American cases with newly diagnosed, previously untreated lung cancer and 270 controls, frequency-matched on age, ethnicity, and sex. Mutagen sensitivity ( 1 chromatid break/cell after short-term bleomycin treatment) was associated with statistically significant elevated risk for lung cancer [odds ration (OR) = 4.3; 95% confidence intervals (CI) = 2.3-7.9]. Wood dust exposure was also a significant predictor of risk (overall OR = 3.5; CI = 1.4-8.6) after controlling for smoking and mutagen sensitivity. When stratified by ethnicity, wood dust exposure was s significant risk factor for African-Americans (OR = 5.5; CI = 1.6-18.9) but not for Mexican-Americans (OR = 2.0; CI = 0.5-8.1). The ORs were 3.8 and 4.8 for non-small cell lung cancer in Mexican-Americans (CI = 1.2-18.5). Stratified analysis suggested evidence of strong interactions between wood dust exposure and both mutagen sensitivity and smoking in lung cancer risk.

    View details for Web of Science ID A1995RU35000003

    View details for PubMedID 8547823

  • MUTAGEN SENSITIVITY AS A RISK FACTOR FOR 2ND MALIGNANT-TUMORS FOLLOWING MALIGNANCIES OF THE UPPER AERODIGESTIVE TRACT JOURNAL OF THE NATIONAL CANCER INSTITUTE SPITZ, M. R., HOQUE, A., TRIZNA, Z., SCHANTZ, S. P., AMOS, C. I., KING, T. M., BONDY, M. L., HONG, W. K., HSU, T. C. 1994; 86 (22): 1681–84

    Abstract

    Second malignant tumors in patients successfully treated for an initial cancer of the upper aerodigestive tract are an important cause of morbidity and mortality. Biologic markers capable of identifying high-risk subgroups of patients who could be targeted for intensive clinical surveillance, therefore, have immense therapeutic and prognostic relevance. We previously demonstrated in a pilot study of 84 patients with cancers of the upper aerodigestive tract that mutagen sensitivity was a significant predictor of risk of developing second malignant tumors.We extended the study to include 278 patients diagnosed with previously untreated cancers of the upper aerodigestive tract from 1987 to August 1993.For each patient, base-line (pretreatment) mutagen sensitivity was measured in vitro in 50 metaphases established from peripheral lymphocyte cultures. Patients with an average of more than 1 chromosomal break/cell were deemed mutagen hypersensitive. Cox proportional hazards analysis was used to predict the risk of developing second malignant tumors associated with mutagen sensitivity.Overall, 44% of the case group exhibited mutagen hypersensitivity. There were no differences in the distribution of mutagen hypersensitivity by site, sex, stage of disease, or smoking status. There were 17 synchronous and 11 metachronous cancers, of which 15 (54%) were smoking-related malignancies. Sixteen (13.1%) of the mutagen-sensitive patients developed second malignant tumors, compared with 12 (7.7%) of the nonsensitive patients. The mean break/cell value (+/- SD) for patients developing second malignant tumors was 1.17 (+/- 0.54), compared with 0.98 (+/- 0.44) for patients with only one cancer (P = .04). Mutagen hypersensitivity conferred a relative risk of 2.67 (95% confidence interval = 1.22-5.79) of developing second malignant tumors.Mutagen hypersensitivity increases the risk of developing second malignant tumors.Future research should focus on the molecular mechanisms underlying mutagen sensitivity.

    View details for DOI 10.1093/jnci/86.22.1681

    View details for Web of Science ID A1994PQ34700011

    View details for PubMedID 7966395

  • VALIDATION OF THE GAIL ET-AL MODEL FOR PREDICTING INDIVIDUAL BREAST-CANCER RISK JOURNAL OF THE NATIONAL CANCER INSTITUTE ATKINS, C. D. 1994; 86 (17): 1350

    View details for DOI 10.1093/jnci/86.17.1350-a

    View details for Web of Science ID A1994PE33100020

    View details for PubMedID 8064895

  • VALIDATION OF A BREAST-CANCER RISK ASSESSMENT MODEL IN WOMEN WITH A POSITIVE FAMILY HISTORY JOURNAL OF THE NATIONAL CANCER INSTITUTE BONDY, M. L., LUSTBADER, E. D., HALABI, S., ROSS, E., VOGEL, V. G. 1994; 86 (8): 620–25

    Abstract

    Gail et al. developed a statistical model for estimating the risk of developing breast cancer in white women screened annually with mammography. This model is used for counseling and for admission to clinical trials.We evaluated the model prospectively in a cohort of women with a family history of breast cancer.We followed women who participated in the American Cancer Society 1987 Texas Breast Screening Project. The model was evaluated by comparing the observed (O) and expected (E) numbers of breast cancers using composite background rates from both the Breast Cancer Detection and Demonstration Project and the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. Data were partitioned by adherence to American Cancer Society screening guidelines.The Gail et al. model predicted the risk well among women who adhered to the American Cancer Society guidelines (O/E = 1.12; 95% confidence interval = 0.75-1.61) but overpredicted risk for women who did not adhere to the guidelines. There was an indication that the model overpredicted risk for women younger than 60 years old and underpredicted risk in women aged 60 years and older.Overall, the Gail et al. model accurately predicts risk in women with a family history of breast cancer and who adhere to American Cancer Society screening guidelines. Thus, the model should be used as it was intended, for women who receive annual mammograms.

    View details for DOI 10.1093/jnci/86.8.620

    View details for Web of Science ID A1994NF21400012

    View details for PubMedID 8003106

  • GERMLINE P53 GENE-MUTATIONS IN SUBSETS OF GLIOMA PATIENTS JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE KYRITSIS, A. P., BONDY, M. L., XIAO, M., BERMAN, E. L., CUNNINGHAM, J. E., LEE, P. S., LEVIN, V. A., SAYA, H. 1994; 86 (5): 344–49

    Abstract

    Heritable germline mutations of the p53 gene have been described in patients with Li-Fraumeni syndrome, occasionally in nonfamilial malignancies such as multifocal osteosarcoma, in a small subgroup of young patients with two or more primary malignancies, and in patients with sporadic breast carcinoma. We recently reported that multifocal gliomas are frequently associated with other primary malignancies, and we hypothesized that genetic alterations may account for this phenomenon.We examined the frequency of germline p53 gene mutations in patients with glioma and either multifocality of lesions, history of an additional primary (different) malignancy, or a family history of cancer.Lymphocytes from 51 glioma patients were analyzed for germline p53 gene mutations using RNA-polymerase chain reaction analysis, single-strand conformation polymorphism, and gene sequencing techniques.Germline p53 gene mutations were detected in six of 19 patients with multifocal glioma, including two with family history of cancer, one with another primary malignancy, and two with all three risk factors; one of four patients with unifocal glioma, another primary malignancy, and a family history of cancer; and two of 15 patients with unifocal glioma and a family history of cancer but no second malignancies. No mutations were detected in the patient with unifocal glioma and another malignancy or in the 12 control patients with unifocal glioma and no second malignancies or family history of cancer. Patients having mutations were younger than other patients in the same group.Germline p53 mutations are frequent in patients with multifocal glioma, glioma and another primary malignancy, and glioma associated with a family history of cancer, particularly if these factors are combined.Relatives at high risk can be identified for genetic counseling, early cancer detection, and possible enrollment in chemoprevention trials.

    View details for DOI 10.1093/jnci/86.5.344

    View details for Web of Science ID A1994MX57200011

    View details for PubMedID 8308926

  • ACCURACY OF FAMILY HISTORY OF CANCER OBTAINED THROUGH INTERVIEWS WITH RELATIVES OF PATIENTS WITH CHILDHOOD SARCOMA JOURNAL OF CLINICAL EPIDEMIOLOGY BONDY, M. L., STROM, S. S., COLOPY, M. W., BROWN, B. W., STRONG, L. C. 1994; 47 (1): 89–96

    Abstract

    The purpose of this study was to determine the accuracy of reporting of invasive cancer by relatives for family studies. First, we attempted to evaluate whether a lower than expected cancer rate found in second-degree relatives of children with soft-tissue sarcoma was a result of underreporting. Second, we evaluated the accuracy of reported cancer in two data sets by comparing reported cancer information with documentation by medical records and death certificates. We obtained medical histories from a primary informant, usually the proband's parent, on 346 first- and 784 second-degree relatives of 68 childhood and adolescent soft-tissue sarcoma patients. To investigate underreporting by the primary informant we conducted an individual interview with each adult relative or proxy. Primary informants reported 22 cancers in first-degree relatives, all confirmed as invasive cancer, and 71 cancers in second-degree relatives with 50 of 67 for which documentation confirmed as invasive. Of 715 individual informants contacted, 15 additional cancers were reported, including 5 confirmed as invasive. The number of first-degree relatives with confirmed invasive cancers was within the expected range; however, the number of cancers in second-degree relatives was below the expected range (observed/expected = 0.51 (54/105.5) 95% confidence interval (CI) = 0.39-0.67). Thus, the lower than expected number of cancers in second-degree relatives was not attributable to underreporting by a single informant or inability to obtain documentation. The overreporting of 25 cancers (24.5%) in second-degree relatives, indicates the need to document all reported cancers.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for DOI 10.1016/0895-4356(94)90037-X

    View details for Web of Science ID A1994MT27800010

    View details for PubMedID 8283198

  • GENETICS OF PRIMARY BRAIN-TUMORS - A REVIEW JOURNAL OF NEURO-ONCOLOGY BONDY, M., WIENCKE, J., WRENSCH, M., KYRITSIS, A. P. 1994; 18 (1): 69–81

    Abstract

    In this review we provide evidence for the existence of genes associated with primary malignant brain tumors. We summarize the current knowledge from studies of familial cancer aggregation, hereditary syndromes, and molecular and cytogenetic studies. The epidemiologic evidence is suggestive but inconclusive for an association between brain tumors and cancers in other family members, including cancers of the breast, lung and colon. Central nervous system (CNS) tumors have been associated with several hereditary syndromes including the Li-Fraumeni cancer family syndrome, neurofibromatosis (types 1 and 2), tuberous sclerosis, nevoid basal cell carcinoma syndrome, familial polyposis, and von Hippel-Lindau disease. Significant studies leading to the recognition of molecular and cytogenetic abnormalities in malignant gliomas are described in detail. The genetic studies conducted thus far suggest a role for inherited susceptibility in some CNS tumors.

    View details for DOI 10.1007/BF01324606

    View details for Web of Science ID A1994NL08400010

    View details for PubMedID 8057137

  • GENETIC SUSCEPTIBILITY TO CANCER CANCER SPITZ, M. R., BONDY, M. L. 1993; 72 (3): 991–95

    Abstract

    For any given level of exposure to a carcinogen, only a proportion of exposed individuals will develop cancer. Interindividual differences in susceptibility at some stage of the carcinogenic process must be postulated. One contributing factor is variation in the activity of metabolizing enzymes responsible for conversion of procarcinogens to proximate carcinogens. There is also a wide spectrum of DNA repair capability within the general population. At one end are the genetic instability syndromes characterized by extreme sensitivity to carcinogenic exposures and high rates of cancer in homozygotes of these traits. Less extreme differences in mutagen sensitivity can be demonstrated by a quantitative assay of chromosome breaks induced by in vitro mutagen exposure. Two case-control studies of patients with previously untreated upper aerodigestive tract cancers have demonstrated mutagen sensitivity to be an independent risk factor for the disease after controlling for the effects of tobacco and alcohol. Mutagen sensitivity also may have prognostic relevance. There was a fourfold elevated risk of developing multiple primary cancers in mutagen-sensitive patients. There are also data suggestive of familial aggregation of cancer in first-degree relatives of mutagen-sensitive patients (twofold risk for having one first-degree relative with cancer and sixfold risk for having two or more relatives with cancer). The preventive implications of identifying markers of carcinogen sensitivity are manifold.

    View details for DOI 10.1002/1097-0142(19930801)72:3+<991::AID-CNCR2820721307>3.0.CO;2-5

    View details for Web of Science ID A1993LQ61800006

    View details for PubMedID 8334675

  • THE TEXAS BREAST SCREENING PROJECT .1. MAMMOGRAPHIC AND CLINICAL-RESULTS SOUTHERN MEDICAL JOURNAL PETERS, G. N., VOGEL, V. G., EVANS, W. P., BONDY, M., HALABI, S., LORD, J., LAVILLE, E. A. 1993; 86 (4): 385–90

    Abstract

    The 1987 Texas Breast Screening Project was designed to educate women about the benefits and safety of mammographic screening. During the 2-week promotion, 109,339 women called toll-free telephone numbers to inquire about the program, and 64,459 (65%) of 99,650 eligible callers had $50 mammograms at 306 participating community radiology centers. Biopsies were obtained for 1,122 women (1.7% of those screened), and the ratio of benign to malignant biopsy results was 4.2:1. Among the women having biopsies, 214 cancers were found (3.3 cancers per 1,000 women screened). Forty-seven percent of the tumors were not palpable, 80% were smaller than 2 cm, and 72% were clinicopathologic stage 0 or I. These results show that women will respond to an invitation to attend mammographic screening, and that community radiology centers can detect large numbers of early, curable breast cancers.

    View details for DOI 10.1097/00007611-199304000-00003

    View details for Web of Science ID A1993KY21000003

    View details for PubMedID 8465213

  • THE TEXAS BREAST SCREENING PROJECT .2. DEMOGRAPHICS, RISK PROFILES, AND HEALTH PRACTICES OF PARTICIPANTS SOUTHERN MEDICAL JOURNAL VOGEL, V. G., BONDY, M., HALABI, S., LORD, J., LAVILLE, E. A. 1993; 86 (4): 391–96

    Abstract

    More than 36,000 of the 64,459 women who had $50 mammograms after a media campaign in 1987 completed a demographic and risk factor questionnaire. The screened women were young and well educated with high annual incomes. Only 32% had had mammograms before 1987. Most women reported that high cost and lack of referral for mammography by their physicians were their reasons for not being screened previously. Publicity promoting the project and the lower cost for mammography were the features of the project that attracted participants. Population-based telephone surveys before and after the project showed a change in attitudes about breast cancer screening. The model used for recruitment in this project can improve compliance with recommendations for regular mammographic screening if charges for screening are reduced. Additional efforts are needed to attract minorities and poor or elderly women to regular breast screening.

    View details for DOI 10.1097/00007611-199304000-00004

    View details for Web of Science ID A1993KY21000004

    View details for PubMedID 8465214

  • ASSOCIATION BETWEEN FAMILY HISTORY OF CANCER AND MUTAGEN SENSITIVITY IN UPPER AERODIGESTIVE TRACT CANCER-PATIENTS CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION BONDY, M. L., SPITZ, M. R., HALABI, S., FUEGER, J. J., SCHANTZ, S. P., SAMPLE, D., HSU, T. C. 1993; 2 (2): 103–6

    Abstract

    This study evaluated the relationship between family history of cancer and bleomycin-induced mutagen sensitivity. The study included 108 patients who registered at The University of Texas M.D. Anderson Cancer Center from June 1987 to June 1991 with histologically confirmed and previously untreated squamous cell carcinoma of the upper aerodigestive tract. All patients underwent the mutagen sensitivity assay and completed a self-administered risk evaluation questionnaire, including a detailed family history. The patients reported having 650 first-degree relatives, including 54 cases with cancers. The patients were classified as mutagen sensitive (> or = 1 chromosome break/cell) or not mutagen sensitive (< or = 0.99 chromosome breaks/cell). Odds ratios (ORs) were calculated to test for significant associations between mutagen sensitivity and family history of cancer. We found a significant OR (OR = 2.63; 95% confidence interval = 1.06-6.53) for patients who were mutagen sensitive and had one first-degree relative affected with cancer. For mutagen-sensitive patients with two or more first-degree relatives affected with cancer, the OR increased to 6.59 (95% confidence interval = 1.69-25.72). Although 88% of the patients were ever smokers, cigarette smoking was not found to be related to mutagen sensitivity. The study findings suggest that patients who have defective DNA repair capability as evidenced by the mutagen sensitivity assay are significantly more likely to report a family history of cancer than patients who are not mutagen sensitive. Further studies are needed to confirm that mutagen-sensitive individuals have inherited an increased risk of cancer.

    View details for Web of Science ID A1993KR07000003

    View details for PubMedID 7682127

  • FACTORS ASSOCIATED WITH PERCEIVED RISK OF BREAST-CANCER AMONG WOMEN ATTENDING A SCREENING-PROGRAM BREAST CANCER RESEARCH AND TREATMENT VERNON, S. W., VOGEL, V. G., HALABI, S., BONDY, M. L. 1993; 28 (2): 137–44

    Abstract

    A person's perception of the risk of, or susceptibility to, developing a disease is believed to be an important determinant of health-related behavior, yet little is known about the determinants of perceived risk. Knowledge of these correlates may be useful in identifying and addressing barriers to performance of health behaviors such as mammography screening. Data collected from over 36,000 women participating in a breast cancer screening program in Texas were used to examine the associations between perceived risk of ever getting breast cancer and a number of demographic factors, health-related behaviors, and risk factors for breast cancer. There was a strong positive association between family history of breast cancer and risk perception (OR = 11.3, CI = 10.34-12.35). Women who reported other risk factors for breast cancer also reported higher perceived risk, but those associations were of lesser magnitude. Age was inversely associated with perceived risk, and black, but not Hispanic, women were more likely to perceive their risk as high compared with white women. Of the health-related behaviors for the early detection of breast cancer, only having had a prior mammogram was associated with perceived risk. Educational interventions to heighten women's awareness of breast cancer risk factors may increase perceived risk in high risk women and influence their decision to undergo screening mammography.

    View details for DOI 10.1007/BF00666426

    View details for Web of Science ID A1993MV18200006

    View details for PubMedID 8173066

  • RECRUITING OLDER WOMEN FOR SCREENING MAMMOGRAPHY CANCER DETECTION AND PREVENTION HALABI, S., VOGEL, V. G., BONDY, M. L., VERNON, S. W. 1993; 17 (3): 359–65

    Abstract

    We compared health behavior and attitudes of older and younger women toward breast cancer screening by using data from the 1987 Texas Breast Screening Project, a community-based, low-cost screening program sponsored by the American Cancer Society, Texas Division. Because age is an important risk factor for breast cancer, the women were categorized into three age groups: 55 to 64 years old, 65 to 74 years old, and 75 years and older. Approximately 67% of the women 75 years and older, 64% of women in the 65 to 74 age group, and 59% of the younger (55 to 64) women had never had mammography. Moreover, only 14% of the women in both the 65 to 74 and 75+ age groups and 19% of the younger women reported having two or more mammographic examinations. Fewer older women (65 to 74 and 75+ age groups) reported having recent clinical breast examination. There were no differences among the age groups in the factors that attracted the women to participate in this screening program; in the three age groups, the most influential factors to participate were media publicity and lower mammography costs. Women in all age groups reported a lack of physician referral and cost as reasons for not previously participating in mammography screening. This study shows that older women are underscreened. Educational programs about the benefits of early detection should target older women because they are at increased risk for breast cancer.

    View details for Web of Science ID A1993LV85100001

    View details for PubMedID 8402722

  • DETECTION OF P53 ALTERATIONS IN HUMAN ASTROCYTOMAS USING FROZEN TISSUE-SECTIONS FOR THE POLYMERASE CHAIN-REACTION JOURNAL OF NEURO-ONCOLOGY OKA, K., BRUNER, J. M., BONDY, M. L., LIGON, K., NISHI, T., DELGIGLIO, A., MOSER, R. P., LEVIN, V. A., SAYA, H. 1993; 16 (2): 125–33

    Abstract

    The polymorphism of amino acid residue 72 on the human p53 tumor-suppressor gene is a useful marker for detecting intragenic loss of heterozygosity (LOH). We examined the LOH of the p53 gene in human malignant astrocytomas by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis using DNA extracted from frozen tissue sections under histologic examination. Eleven of 16 informative cases (69%) of the malignant astrocytomas were found to have LOH in the p53 gene. Sequential frozen sections were analyzed by immunohistochemistry using anti-p53 antibody PAb1801 to detect overexpression of the p53 protein, which is presumably altered if it is detectable. Ten of the 11 cases that had LOH of the p53 gene overexpressed the p53 protein. Moreover, 4 of the 11 patients with LOH of the p53 gene developed a second neoplasm in addition to an astrocytoma, possibly indicating genetic instability in these patients. These data suggest that alterations of the p53 gene may play an important role in the genesis of malignant astrocytoma. The combination of the PCR-RFLP method and immunohistochemical analysis using frozen tissue sections is a practical diagnostic tool for examination of human malignancies, including astrocytomas. astrocytomas.

    View details for DOI 10.1007/BF01324699

    View details for Web of Science ID A1993MA01900005

    View details for PubMedID 7904621

  • ENVIRONMENTAL RISK-FACTORS FOR PRIMARY MALIGNANT BRAIN-TUMORS - A REVIEW JOURNAL OF NEURO-ONCOLOGY WRENSCH, M., BONDY, M. L., WIENCKE, J., YOST, M. 1993; 17 (1): 47–64

    View details for DOI 10.1007/BF01054274

    View details for Web of Science ID A1993MM00400008

    View details for PubMedID 8120572

  • SEGREGATION ANALYSIS OF CANCER IN FAMILIES OF CHILDHOOD SOFT-TISSUE-SARCOMA PATIENTS AMERICAN JOURNAL OF HUMAN GENETICS LUSTBADER, E. D., WILLIAMS, W. R., BONDY, M. L., STROM, S., STRONG, L. C. 1992; 51 (2): 344–56

    Abstract

    This paper presents the analysis of familial cancer data collected in a hospital-based study of 159 childhood soft-tissue-sarcoma patients. Two different statistical models detected excess aggregation of cancer, which could be explained by a rare dominant gene. For each kindred, we estimated the probability of the observed cancer distribution under the dominant-gene model and identified 12 families that are the most likely to be segregating the gene. Two of those families have confirmed germ-line mutations in the p53 tumor-suppressor gene. The relative risk of affection for children who are gene carriers was estimated to be 100 times the background rate. Females were found to have a slightly higher age-specific penetrance, but maternal and paternal lineages made equal contributions to the evidence in favor of the dominant gene. The proband's histology, ethnicity, and age at diagnosis were evaluated to determine whether any of these altered the probability of affection in family members. Only embryonal rhabdomyosarcoma was found to be a significant covariate under the dominant-gene model. While molecular genetic studies of familial cancer will eventually provide answers to the questions of genetic heterogeneity, age- and site-specific penetrance, mutation rates, and gene frequency, information from statistical models is useful for setting priorities and defining hypotheses.

    View details for Web of Science ID A1992JF77600014

    View details for PubMedID 1642235

    View details for PubMedCentralID PMC1682662

  • LOW INCIDENCE OF FAMILIAL BREAST-CANCER AMONG HISPANIC WOMEN CANCER CAUSES & CONTROL BONDY, M. L., SPITZ, M. R., HALABI, S., FUEGER, J. J., VOGEL, V. G. 1992; 3 (4): 377–82

    Abstract

    There is a paucity of data on familial patterns of breast cancer among minority populations. This study compared the frequency of cancer in 1,095 first-degree relatives of 50 White, 46 Black, and 49 Hispanic breast-cancer patients referred to The University of Texas M.D. Anderson Cancer Center (United States). Family histories of cancer were derived from a self-administered questionnaire on risk factors. Expected numbers of cancers were calculated from the Connecticut Tumor Registry for White and Black relatives and from the New Mexico Tumor Registry for Hispanic relatives. Family history of a first-degree relative with breast cancer was the most important risk factor for both Black and White patients. Significantly elevated standardized incidence ratios (SIR) for breast cancer were noted among White (SIR = 4.5, 95 percent confidence interval [CI] = 1.2-11.4) and Black (SIR = 4.1, CI = 1.1-10.4) relatives younger than age 45. Despite the small number of Black patients, the combined effect of family history of breast cancer and the relative's age at diagnosis (under 45 years) was associated with an SIR of 7.1 (CI = 1.9-18.1). A deficit of cancer was noted in Hispanic women; only one patient reported having a first-degree relative with breast cancer. These findings, although based on small numbers, suggest that Hispanics have a lower rate of familial breast cancer than Whites and Blacks, and that they may possess protective factors that reduce their risk for breast cancer.

    View details for DOI 10.1007/BF00146892

    View details for Web of Science ID A1992JC10800011

    View details for PubMedID 1617126

  • WOMEN WITH A HISTORY OF BREAST-CANCER JOURNAL OF THE NATIONAL CANCER INSTITUTE VOGEL, V. G., BONDY, M. 1992; 84 (9): 724–25

    View details for DOI 10.1093/jnci/84.9.724

    View details for Web of Science ID A1992HR76300023

    View details for PubMedID 1569608

  • RADIOTHERAPY DURING PREGNANCY FOR CLINICAL STAGES IA-IIA HODGKINS-DISEASE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS WOO, S. Y., FULLER, L. M., CUNDIFF, J. H., BONDY, M. L., HAGEMEISTER, F. B., MCLAUGHLIN, P., VELASQUEZ, W. S., SWAN, F., RODRIGUEZ, M. A., CABANILLAS, F., ALLEN, P. K., CARPENTER, R. J. 1992; 23 (2): 407–12

    Abstract

    Between 1956 and 1990, 775 women were treated for Hodgkin's disease at The University of Texas M.D. Anderson Cancer Center. Of these, 25 (3.2%) were pregnant at diagnosis. Seven of these women were in the first trimester, 10 in the second, and eight in the third. Prior to treatment, three women in the third trimester had normal deliveries, and six patients in the first trimester had abortions. Sixteen patients received radiotherapy for supradiaphragmatic presentations during their pregnancies. All these patients had nodular sclerosing Hodgkin's disease: Two had clinical stage IA presentations and 14 had clinical stage IIA. In two patients radiotherapy (35 Gy) was limited to the neck, three patients were treated definitively to the neck and mediastinum (40 Gy), and 11 patients received mantle irradiation (40 Gy). Four to five half-value layers of lead were used to shield the uterus during radiotherapy. The dose to the fetus was estimated individually in nine patients, using a combination of an Alderson-Rando and a water phantom. The estimated total dose to the mid-fetus ranged from 1.4 to 5.5 cGy for treatment with 6 MV photons, and from 10 to 13.6 cGy for Cobalt 60. All 16 patients subsequently delivered full-term, normal infants. Following delivery, all of the patients had further staging procedures; eight received additional treatment. Subsequently, the disease relapsed in four patients; two eventually died of Hodgkin's disease. The 10-year determinant and overall survival rates were 83% and 71%, respectively. Currently, all offspring are physically and mentally normal, and none has developed a malignancy. Radiotherapy is an appropriate initial treatment for supradiaphragmatic presentations of Hodgkin's disease during the second and third trimesters of pregnancy, provided special attention is paid to treatment and shielding techniques. The outcome for women treated with irradiation for clinical stage I and II Hodgkin's disease during pregnancy has not been shown to be adversely affected by pregnancy, and after the first 8 weeks of gestation, the risk to the fetus appears to be minimal.

    View details for DOI 10.1016/0360-3016(92)90761-6

    View details for Web of Science ID A1992HW22500022

    View details for PubMedID 1587764

  • SEGREGATION ANALYSIS OF 159 SOFT-TISSUE SARCOMA KINDREDS - COMPARISON OF FIXED AND SEQUENTIAL SAMPLING SCHEMES GENETIC EPIDEMIOLOGY BONDY, M. L., LUSTBADER, E. D., STROM, S. S., STRONG, L. C. 1992; 9 (5): 291–304

    Abstract

    In this study we compared parameter estimates and model hypotheses in pedigree data collected by fixed sampling with estimates and hypotheses derived by sequential sampling. Employing a fixed sampling scheme, we previously analyzed data on relatives of 159 childhood sarcoma patients. We have now extracted from that data set individuals who would have been included in a sequentially sampled study. We applied segregation analysis to the truncated data, to determine the mode of inheritance and major locus parameter estimates. With data from both sampling schemes we made a family-by-family comparison to determine each family's contribution to a major gene model. The two sampling schemes yielded similar results: we detected segregation of a dominant major gene and obtained similar major locus parameter estimates. However, the sequential sampling scheme derived these conclusions from data on 982 relatives rather than the 2,451 ascertained in the fixed sampling scheme. The sequential sampling scheme failed to identify only one of the kindreds likely to be segregating the gene. For this data set, the sequential sampling scheme would have provided an efficient mechanism to discriminate genetic hypotheses and would have permitted focus of resources on the specific kindreds likely to segregate a major gene.

    View details for DOI 10.1002/gepi.1370090502

    View details for Web of Science ID A1992JW00400001

    View details for PubMedID 1427019

  • IDENTIFICATION OF WOMEN AT INCREASED RISK FOR BREAST-CANCER IN A POPULATION-BASED SCREENING-PROGRAM CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION BONDY, M. L., VOGEL, V. G., HALABI, S., LUSTBADER, E. D. 1992; 1 (2): 143–47

    Abstract

    A multivariate model to assess breast cancer risk was developed by Gail et al. (M. H. Gail, L. A. Brinton, D. B. Byar, D. K. Corle, S. B. Green, C. Schairer, and J. J. Mulvihill, J. Natl. Cancer Inst., 81: 1879-1886, 1989) based on data analysis of the Breast Cancer Detection and Demonstration Project. We evaluated the model's usefulness for assigning women to risk groups for counseling and follow-up by applying it to the 1987 Texas Breast Screening Project data. We identified 3165 women with one or more first-degree relatives affected with breast cancer. The mean risk score for the group was 3.3 (range, 2.7-11.8), indicating a greater than 3-fold elevated risk. The mean risk score for the remaining 27,439 women without affected first-degree relatives was 1.5 (range, 1.24-3.2). Risk perception was found to be a motivator for participation. Women with a risk score greater than 5 perceived themselves to be at high risk for breast cancer. The perception of risk was related to the type of affected first-degree relatives: 80.0% of the women with three affected first-degree relatives and 71.5% of women whose mother and sister were both affected with breast cancer perceived themselves to be at high risk. The Gail model is potentially useful in the clinical setting because women at high risk for breast cancer can be entered into etiological studies, enrolled in primary prevention trials, or referred to programs seeking to improve compliance with screening mammography. The Gail model needs validation, but it is useful for estimating the risk of breast cancer in large populations.

    View details for Web of Science ID A1992HN95100008

    View details for PubMedID 1306097

  • COMPARISON OF ACCURACY OF CANCER INFORMATION IN A FAMILY STUDY OF CHILDHOOD SOFT-TISSUE SARCOMA BONDY, M. L., STROM, S. S., COLOPY, M. W., BROWN, B. W., STRONG, L. C. AMER J EPIDEMIOLOGY. 1991: 766
  • GENETIC EPIDEMIOLOGY OF CHILDHOOD BRAIN-TUMORS GENETIC EPIDEMIOLOGY BONDY, M. L., LUSTBADER, E. D., BUFFLER, P. A., SCHULL, W. J., HARDY, R. J., STRONG, L. C. 1991; 8 (4): 253–67

    Abstract

    The study goal was to determine the genetic (heritable) contribution to childhood brain tumors (CBT) which cause nearly one quarter of all childhood cancer deaths. Their etiology remains unknown, but previous studies have suggested a proportion of CBT may be heritable. In this study we collected family histories of 243 confirmed CBT patients referred to The University of Texas M. D. Anderson Cancer Center between the years 1944 and 1983, diagnosed before age 15, and residents of the United States or Canada. Family histories were obtained for all the probands' first degree relatives (parents, siblings, and offspring) and extended to include selected second degree relatives (aunts, uncles, grandparents) using sequential sampling. To determine if these CBT families exhibited excess cancer, we compared their cancer experience to age-, race-, sex-, and calendar-year specific rates from the Connecticut Tumor Registry. No cancer excess was observed among 1,099 first and second degree relatives [39 cancers observed (O) and 44 expected (E) for a standardized incidence ratio (SIR) of 0.88]. For colon cancer, although small numbers, five cases were observed among the probands' first degree relatives with 1.6 expected, for a significant SIR of 3.10. Segregation analysis demonstrated that chance alone could not account for the observed cancer distribution with a multifactorial model providing the best overall explanation of the data. Overall, heredity played a role in the etiology of CBT in 4% of the study families: four (1.7%) due to known hereditary syndromes (nevoid basal cell carcinoma syndrome and von Recklinghausens neurofibromatosis--NF-1), four (1.7%) with multifactorial inheritance, and two additional families with cancers aggregating similar to the clinical criteria described for the Li-Fraumeni cancer family syndrome.

    View details for DOI 10.1002/gepi.1370080406

    View details for Web of Science ID A1991GN91500005

    View details for PubMedID 1756948

  • BRAIN CANCER AND OCCUPATIONS - RESULTS OF A 16-YEAR DECEDENT CASE-COMPARISON STUDY OF CNS CANCER IN GALVESTON-COUNTY, TEXAS, 1964-1979 BONDY, M., BUFFLER, P., WOOD, S. JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH. 1982: 568