@article{fde9febdfc9b42228f0c73060ecd66af,
title = "Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European Cohort",
abstract = "Background: Evidence on associations between self-reported diabetes mellitus, diabetes duration, age at diabetes diagnosis, insulin treatment, and risk of biliary tract cancer (BTC) and hepatocellular carcinoma (HCC), independent of general and abdominal obesity is scarce. Patients and methods: We conducted a prospective analysis in the EPIC-cohort study among 363 426 participants with self-reported diabetes data. Multivariable adjusted relative risks and 95% confidence intervals were estimated from Cox regression models. In a nested case-control subset, analyses were carried out in HCV/HBV-negative individuals. Results: During 8.5 years of follow-up, 204 BTC cases [including 75 gallbladder cancer (GBC) cases], and 176 HCC cases were identified. Independent of body mass index and waist-to-height ratio diabetes status was associated with higher risk of BTC and HCC [1.77 (1.00-3.13) and 2.17 (1.36-3.47)]. For BTC, the risk seemed to be higher in participants with shorter diabetes duration and those not treated with insulin. Regarding cancer subsites, diabetes was only associated with GBC [2.72 (1.17-6.31)]. The risk for HCC was particularly higher in participants treated with insulin. The results were not appreciably different in HCV/HBV-negative individuals. Conclusion(s): This study supports the hypothesis that diabetes is a risk factor for BTC (particularly GBC) and HCC. Further research is required to establish whether diabetes treatment or duration is associated with these cancers.",
keywords = "Biliary tract neoplasms, Diabetes duration, Diabetes mellitus, Gallbladder neoplasms, Hepatocellular carcinoma, Insulin treatment",
author = "S. Schlesinger and K. Aleksandrova and T. Pischon and M. Jenab and V. Fedirko and E. Trepo and K. Overvad and N. Roswall and A. Tj{\o}nneland and Boutron-Ruault, {M. C.} and G. Fagherazzi and A. Racine and R. Kaaks and Grote, {V. A.} and H. Boeing and A. Trichopoulou and M. Pantzalis and M. Kritikou and A. Mattiello and S. Sieri and C. Sacerdote and D. Palli and R. Tumino and Peeters, {P. H.} and Bueno-de-Mesquita, {H. B.} and E. Weiderpass and Quir{\'o}s, {J. R.} and R. Zamora-Ros and S{\'a}nchez, {M. J.} and L. Arriola and E. Ardanaz and Tormo, {M. J.} and P. Nilsson and B. Lindkvist and M. Sund and O. Rolandsson and Khaw, {K. T.} and N. Wareham and Travis, {R. C.} and E. Riboli and U. N{\"o}thlings",
note = "Funding Information: This work was supported by the Federal Ministry of Education and Research, the German Research Foundation, Excellence Cluster Inflammation at Interfaces (EXC306 and EXC306/2), grants from the German Research Foundation (DFG NO446/7-1) (Germany); and the French National Cancer Institute (L{\textquoteright}Institut National du Cancer; INCA) (grant number 2009-139). The coordination of EPIC is financially supported by the European Commission (DG-SANCO); and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer; Institut Gustave Roussy; Mutuelle G{\'e}n{\'e}rale de l{\textquoteright}Education Nationale; and Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum; the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity (Greece); Italian Association for Research on Cancer (AIRC); National Research Council; and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS); Netherlands Cancer Registry (NKR); LK Research Funds; Dutch Prevention Funds; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); and Statistics Netherlands (The Netherlands); European Research Council (ERC) (grant number ERC-2009-AdG 232997) and Nordforsk; and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS); Regional Governments of Andaluc{\'i}a, Asturias, Basque Country, Murcia (No. 6236) and Navarra; and ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society; Swedish Scientific Council; and Regional Government of Sk{\aa}ne and V{\"a}sterbotten (Sweden); Cancer Research UK; Medical Research Council; Stroke Association; British Heart Foundation; Department of Health; Food Standards Agency; and Wellcome Trust (UK).",
year = "2013",
month = sep,
doi = "10.1093/annonc/mdt204",
language = "English",
volume = "24",
pages = "2449--2455",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Elsevier Ltd.",
number = "9",
}