Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort

• Published in: Annals of oncology Vol. 24; no. 9; pp. 2449 - 2455
• Main Authors: Schlesinger, S., Aleksandrova, K., Pischon, T., Jenab, M., Fedirko, V., Trepo, E., Overvad, K., Roswall, N., Tjønneland, A., Boutron-Ruault, M.C., Fagherazzi, G., Racine, A., Kaaks, R., Grote, V.A., Boeing, H., Trichopoulou, A., Pantzalis, M., Kritikou, M., Mattiello, A., Sieri, S., Sacerdote, C., Palli, D., Tumino, R., Peeters, P.H., Bueno-de-Mesquita, H.B., Weiderpass, E., Quirós, J.R., Zamora-Ros, R., Sánchez, M.J., Arriola, L., Ardanaz, E., Tormo, M.J., Nilsson, P., Lindkvist, B., Sund, M., Rolandsson, O., Khaw, K.T., Wareham, N., Travis, R.C., Riboli, E., Nöthlings, U.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2013; Oxford University Press
• Subjects: Antineoplastic agents; Biliary tract neoplasms; Biliary Tract Neoplasms - complications; Biliary Tract Neoplasms - epidemiology; Biological and medical sciences; Body Composition; Body Mass Index; Cancer and Oncology; Cancer och onkologi; Carcinoma, Hepatocellular - complications; Carcinoma, Hepatocellular - epidemiology; Case-Control Studies; Clinical Medicine; Cohort Studies; Diabetes duration; Diabetes mellitus; Diabetes Mellitus - drug therapy; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinology and Diabetes; Endocrinopathies; Endokrinologi och diabetes; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Europe; Female; Gallbladder neoplasms; Gastroenterology. Liver. Pancreas. Abdomen; Hepatocellular carcinoma; Humans; Insulin - therapeutic use; Insulin treatment; Klinisk medicin; Liver Neoplasms - complications; Liver Neoplasms - epidemiology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Obesity, Abdominal - epidemiology; Original; Pharmacology. Drug treatments; Prospective Studies; Risk Factors; Self Report; Tumors; Europe; diabetes mellitus; diabetes duration; insulin treatment; gallbladder neoplasms; biliary tract neoplasms; hepatocellular carcinoma; Endocrinopathy; Biliary tract; Pancreatic hormone; Digestive system; Bile duct cancer; Diabetes mellitus; Hepatic disease; Hepatocellular carcinoma; Malignant tumor; Biliary tract disease; Treatment duration; Insulin; Liver cancer; Treatment; Cohort study; Risk factor; Digestive diseases; Gallbladder; Public health; Cancer
• ISSN: 0923-7534; 1569-8041; 1569-8041
• DOI: 10.1093/annonc/mdt204

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.
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.
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.
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.