Jingru Yu

All Publications

• Risk of malignant lymphomas in patients with inflammatory bowel disease: a population-based cohort study BMJ OPEN GASTROENTEROLOGY Yu, J., Refsum, E., Wieszczy, P., Helsingen, L. M., Perrin, V., Hogden, A., Loberg, M., Blom, J., Bretthauer, M., Adami, H., Ye, W., Kalager, M. 2023; 10 (1)

  Abstract

  To estimate the risk of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) in patients with inflammatory bowel disease (IBD).We undertook a two-country population cohort study with all patients diagnosed with IBD in Norway and Sweden from 1987 and 1993 through 2015 and 2016, respectively, and analysed the risk of NHL and HL. In Sweden, we also analysed prescriptions of thiopurines and anti-tumour necrosis factor (TNF)-α therapy from 2005. We calculated standardised incidence ratios (SIRs) with 95% CIs using the general populations as reference.Among 131 492 patients with IBD with a medium follow-up of 9.6 years, we identified 369 cases of NHL and 44 cases of HL. The SIR of NHL was 1.3 (95% CI 1.1 to 1.5) in ulcerative colitis and 1.4 (95% CI 1.2 to 1.7) in Crohn's disease. We found no compelling heterogeneity in analyses stratified by patient characteristics. We found a similar pattern and magnitude of excess risks for HL. At 10 years, cumulative incidence was 0.26% (95% CI 0.23% to 0.30%) and 0.06% (95% CI 0.04% to 0.08%) for NHL and HL, respectively. Higher excess risks were found among patients with NHL with concomitant primary sclerosing cholangitis (SIR 3.4; 95% CI 2.1 to 5.2) and in those prescribed thiopurines alone (SIR 2.8; 95% CI 1.4 to 5.7) or with anti-TNF-α agents (SIR 5.7; 95% CI 2.7 to 11.9).Patients with IBD have a statistically significant increased risk of malignant lymphomas compared with the general population, but the absolute risk remains low.

  View details for DOI 10.1136/bmjgast-2022-001037

  View details for Web of Science ID 000983830000001

  View details for PubMedID 37142293

  View details for PubMedCentralID PMC10163486

• Genome-Wide DNA Methylation Identifies Distinct Subgroups of Vulvovaginal Mesenchymal Neoplasia Neil, A., Howitt, B., Yu, J., Bennett, J., Pinto, A., Quick, C., Neville, G., Nucci, M., Chapel, D., Heilbroner, L., Wang, A., Yao, Y., Ahmann, L., Gu, W., Parra-Herran, C. ELSEVIER SCIENCE INC. 2023: S960-S961

  View details for Web of Science ID 000990969802101

• Poor dental health and risk of pancreatic cancer: a nationwide registry-based cohort study in Sweden, 2009-2016. British journal of cancer Yu, J., Ploner, A., Chen, M. S., Zhang, J., Sandborgh-Englund, G., Ye, W. 2022

  Abstract

  BACKGROUND: Previous studies have reported inconsistent results regarding the association between poor dental health and pancreatic cancer risk. This study aimed to assess this association using a well-functioning nationwide dental health registry in Sweden.METHODS: Information of exposures (dental caries, root canal infection, mild inflammation, and periodontitis; the number of teeth) was ascertained from the Swedish Dental Health Register, and occurrence of pancreatic cancer was identified from both cancer and cause of death registries. Hazard ratios (HRs) were estimated using Cox models.RESULTS: During a median of 7.2 years of follow-up, 10,081 pancreatic cancers were identified among 5,889,441 individuals. Compared with the healthy status, a higher risk of pancreatic cancer was observed in individuals with root canal infection, mild inflammation, and periodontitis in the <50 age group (P for trend <0.001). In the 50-70 age group, only the subgroup with periodontitis had an excess risk (multivariable-adjusted HR=1.20, 95% confidence interval [CI] 1.11-1.29). No positive association with statistical significance was observed in the 70+ age group. Individuals with fewer teeth tended to have a higher risk in all age groups.CONCLUSIONS: Our results confirmed the association between poor dental health and pancreatic cancer risk, which warrants further studies on underlying mechanisms.

  View details for DOI 10.1038/s41416-022-02018-8

  View details for PubMedID 36273086

• Poor Oral Health and Esophageal Cancer Risk: A Nationwide Cohort Study CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Zhang, J., Bellocco, R., Sandborgh-Englund, G., Yu, J., Chen, M., Ye, W. 2022; 31 (7): 1418-1425

  Abstract

  Previous research indicates that poor dental health increases risks for certain types of cancers, including esophageal cancer. This study aimed to investigate the association with esophageal cancer using Swedish Dental Health Register.This is a prospective cohort study. The exposures were dental diagnoses classified into healthy, caries, root canal infection, mild inflammation, and periodontitis, as well as number of remaining teeth, at baseline and during multiple visits. The outcome was the incidence of esophageal cancer, which was further divided into esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Cox proportional hazards models were used to estimate hazard ratios (HR) and its corresponding confidence intervals (CI).A total of 5,042,303 individuals were included in the study and 1,259 EAC and 758 ESCC cases were identified. Root canal infection at baseline was associated with 41% higher risk for EAC (HR, 1.41; 95% CI, 1.10-1.82), whereas periodontitis at baseline was linked to 32% and 45% higher risks for respective histopathological subtypes (HR for EAC, 1.32; 95% CI, 1.13-1.53; HR for ESCC, 1.45; 95% CI, 1.20-1.75). Fewer remaining teeth at baseline also increased the risks for both histopathological types of esophageal cancer, with a dose-response effect (Ptrend < 0.01). Cox regression analyses with time-varying exposures corroborated the above-mentioned results.Impaired dental health before cancer diagnosis is associated with excess risks for both histopathological subtypes of esophageal cancer.Our study provided corroborating evidence for the association between poor oral health and esophageal cancer risk.

  View details for DOI 10.1158/1055-9965.EPI-22-0151

  View details for Web of Science ID 000823304200001

  View details for PubMedID 35477184

• Inflammatory bowel disease and risk of adenocarcinoma and neuroendocrine tumors in the small bowel ANNALS OF ONCOLOGY Yu, J., Refsum, E., Perrin, Helsingen, L. M., Wieszczy, P., Loberg, M., Bretthauer, M., Adami, H. O., Ye, W., Blom, J., Kalager, M. 2022; 33 (6): 649-656

  Abstract

  Uncertainty prevails about the magnitude of excess risk of small bowel cancer in patients with inflammatory bowel disease (IBD).To quantify the risk of small bowel adenocarcinoma and neuroendocrine tumors in patients with ulcerative colitis (UC) and Crohn's disease (CD), we undertook a population-based cohort study of all patients with IBD diagnosed in Norway and Sweden from 1987 to 2016. Patients were followed through linkage to national registers. We calculated standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) of small bowel adenocarcinomas and neuroendocrine tumors for patients with CD and UC. We excluded the first year of follow-up to reduce reverse causality.Among 142 008 patients with a median follow-up of 10.0 years, we identified 66 adenocarcinomas and 57 neuroendocrine tumors in the small bowel. The SIR of small bowel adenocarcinoma was 8.3 (95% CI 5.9-11.3) in CD and 2.0 (95% CI 1.2-3.1) in UC. The incidence rates of adenocarcinomas were highest in CD with stricturing disease and extent limited to the small bowel, at 14.7 (95% CI 8.2-24.2) and 15.8 (95% CI 8.4-27.0) per 100 000 person-years, respectively. The SIR of neuroendocrine tumors was 2.5 (95% CI 1.5-3.9) in CD and 2.0 (95% CI 1.4-2.8) in UC.Patients with CD experienced an eightfold increased risk of small bowel adenocarcinomas, patients with both UC and CD experienced an about twofold increased risk of neuroendocrine tumors, and patients with UC experienced a twofold increased risk of small bowel adenocarcinoma. The small absolute excess cancer risk suggests that active surveillance to diagnose small intestinal cancer early is unlikely to be cost-effective.

  View details for DOI 10.1016/j.annonc.2022.02.226

  View details for Web of Science ID 000806396900010

  View details for PubMedID 35276334

• Risk of hepato-pancreato-biliary cancer is increased by primary sclerosing cholangitis in patients with inflammatory bowel disease: A population-based cohort study. United European gastroenterology journal Yu, J., Refsum, E., Helsingen, L. M., Folseraas, T., Ploner, A., Wieszczy, P., Barua, I., Jodal, H. C., Melum, E., Løberg, M., Blom, J., Bretthauer, M., Adami, H. O., Kalager, M., Ye, W. 2022; 10 (2): 212-224

  Abstract

  There is continued uncertainty regarding the risks of hepato-pancreato-biliary cancers in patients with inflammatory bowel disease (IBD) with or without concomitant primary sclerosing cholangitis (PSC).To give updated estimates on risk of hepato-pancreato-biliary cancers in patients with IBD, including pancreatic cancer, hepatocellular carcinoma, gall bladder cancer, and intra - and extrahepatic cholangiocarcinoma.In a population-based cohort study, we included all patients diagnosed with IBD in Norway and Sweden from 1987 to 2016. The cohort comprised of 141,960 patients, identified through hospital databases and the National Patient Register. Participants were followed through linkage to national cancer, cause of death, and population registries. We calculated absolute risk and standardized incidence ratios (SIRs) of hepato-pancreato-biliary cancers by PSC and other clinical characteristics.Of the 141,960 IBD patients, 3.2% were diagnosed with PSC. During a median follow-up of 10.0 years, we identified 443 biliary tract cancers (SIR 5.2, 95% confidence interval [CI] 4.8-5.7), 161 hepatocellular carcinomas (SIR 2.4, 95% CI 2.0-2.7) and 282 pancreatic cancers (SIR 1.3, 95% CI 1.2-1.5). The relative risks were considerably higher in PSC-IBD patients, with SIR of 140 (95% CI 123-159) for biliary tract, 38.6 (95% CI 29.2-50.0) for hepatocellular, and 9.0 (95% CI 6.3-12.6) for pancreatic cancer. The SIRs were still slightly increased in non-PSC-IBD patients, compared to the general population. For biliary tract cancer, the cumulative probability at 25 years was 15.6% in PSC-IBD patients, and 0.4% in non-PSC-IBD patients.The dramatically increased risks of hepato-pancreato-biliary cancers in PSC-IBD patients support periodic surveillance for these malignancies. While much lower, the excess relative risks in non-PSC-IBD patients were not trivial compared to non-IBD related risk factors.

  View details for DOI 10.1002/ueg2.12204

  View details for PubMedID 35107865

  View details for PubMedCentralID PMC8911542

• Burden of pancreatic cancer along with attributable risk factors in Europe between 1990 and 2019, and projections until 2039. International journal of cancer Yu, J., Yang, X., He, W., Ye, W. 2021; 149 (5): 993-1001

  Abstract

  Projecting the burden of pancreatic cancer over time provides essential information to effectively plan measures for its management and prevention. Here, we obtained data from the Global Burden of Disease (GBD) Study between 1990 and 2019, to model how pancreatic cancer will affect the 27 countries of the European Union (EU) plus the United Kingdom (the pre-Brexit EU-28) until 2039 by conducting the Bayesian age-period-cohort analysis. The number of new pancreatic cancer cases in the EU-28 was 59 000 in 1990, 109 000 in 2019 and projected to be 147 000 in 2039. This corresponded to 60 000, 109 000 and 155 000 for deaths, and a loss of 1.3 million, 2.0 million and 2.7 million for disability-adjusted life years (DALYs), respectively. The most pronounced increase of the crude incidence rate was observed and projected to be in the population older than 80 years. The age-standardized rate (ASR) of incidence, however, increased from 8.6 to 10.1 per 100 000 person-years during 1990-2019 but was projected to remain stable during 2019-2039. At the same time, our models only predicted a mild increase in the ASR of mortality until 2039. The fraction of pancreatic cancer mortality attributable to tobacco consumption decreased during 1990-2019, but we found upward trends for the attributable fractions for high fasting plasma glucose and high body mass index. In conclusion, a substantial increase in counts of incidence, mortality and DALYs lost of pancreatic cancer in the EU-28 is projected over the next two decades, which indicates the need for future health policies and interventions.

  View details for DOI 10.1002/ijc.33617

  View details for PubMedID 33937984

• Plasma protein biomarkers for early detection of pancreatic ductal adenocarcinoma INTERNATIONAL JOURNAL OF CANCER Yu, J., Ploner, A., Kordes, M., Lohr, M., Nilsson, M., de Maturana, M., Estudillo, L., Renz, H., Carrato, A., Molero, X., Real, F. X., Malats, N., Ye, W. 2021; 148 (8): 2048-2058

  Abstract

  Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, mainly due to late diagnosis at advanced tumor stages. In this study, we aimed to identify plasma protein biomarkers for early detection of PDAC. Totally, 135 PDAC patients (early PDAC, Stage I/II, n = 71; advanced PDAC, Stage III/IV, n = 64), 13 benign lesions/chronic pancreatitis patients and 72 healthy individuals, with corresponding plasma samples from a case-control study in Sweden were included. A proximity extension assay was used to detect 92 cancer-related proteins, and an enzyme-linked immunosorbent assay/electrochemiluminescence immunoassay was used to detect CA19-9. Predictive features were selected from these 93 candidate proteins and three covariates in the Swedish participants, and then validated in Spanish participants, including 37 early PDAC patients, 38 advanced PDAC patients, 19 chronic pancreatitis patients and 36 healthy controls. A panel of eight proteins discriminating early PDAC from healthy individuals was identified, and the cross-validated area under the curves (AUCs) were 0.85 (95% confidence interval, 95% CI, 0.78-0.91) and 0.81 (95% CI, 0.70-0.92) in the Swedish and Spanish participants, respectively. Another eight-protein panel was predictive for classifying advanced PDAC from healthy controls in two populations, with cross-validated AUCs of 0.89 (95% CI, 0.83-0.95) and 0.90 (95% CI, 0.83-0.98), respectively. In conclusion, eight protein biomarkers were identified and externally validated, potentially allowing early detection of PDAC patients if validated in additional prospective studies.

  View details for DOI 10.1002/ijc.33464

  View details for Web of Science ID 000607653900001

  View details for PubMedID 33411965