Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium

• Published in: Annals of oncology Vol. 25; no. 10; pp. 2065 - 2072
• Main Authors: Bosetti, C., Rosato, V., Li, D., Silverman, D., Petersen, G.M., Bracci, P.M., Neale, R.E., Muscat, J., Anderson, K., Gallinger, S., Olson, S.H., Miller, A.B., Bas Bueno-de-Mesquita, H., Scelo, G., Janout, V., Holcatova, I., Lagiou, P., Serraino, D., Lucenteforte, E., Fabianova, E., Baghurst, P.A., Zatonski, W., Foretova, L., Fontham, E., Bamlet, W.R., Holly, E.A., Negri, E., Hassan, M., Prizment, A., Cotterchio, M., Cleary, S., Kurtz, R.C., Maisonneuve, P., Trichopoulos, D., Polesel, J., Duell, E.J., Boffetta, P., La Vecchia, C., Ghadirian, P.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.10.2014; Oxford University Press
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; Case-Control Studies; case–control study; diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - pathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Hypoglycemic Agents - therapeutic use; Insulin; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Logistic Models; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); oral antidiabetics; Original; pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - epidemiology; Pancreatic Neoplasms - etiology; Pancreatic Neoplasms - pathology; Pharmacology. Drug treatments; pooled analysis; Risk Factors; Smoking; Tumors; case–control study; pancreatic cancer; pooled analysis; oral antidiabetics; insulin; diabetes; Endocrinopathy; Human; Drug; Pancreatic hormone; Diabetes mellitus; Oral administration; Malignant tumor; Case control study; Risk analysis; Insulin; Hypoglycemic agent; case-control study; Pancreas cancer; Digestive diseases; Cancer; Pancreatic disease; International
• ISSN: 0923-7534; 1569-8041; 1569-8041
• DOI: 10.1093/annonc/mdu276

Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time–risk relationship are unclear, and there is limited information on the role of antidiabetic medications. We analyzed individual-level data from 15 case–control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72–2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03–1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14–0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75–8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53–1.70, for ≥15 years). This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration–risk relationship.