Diabetes, antidiabetic medications and pancreatic cancer risk: an analysis from the international pancreatic cancer case-control consortium.
Ann Oncol. 2014 Jul 23. Epub 2014 Jul 23. PMID: 25057164
BACKGROUND: 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.
PATIENTS AND METHODS: 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 RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes two or more years before cancer diagnosis (or interview, for controls), corresponding to an odds ratio (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 1.17-2.03). 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 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).
CONCLUSION: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows 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 risk of pancreatic cancer risk, whereas insulin showed an inconsistent duration-risk relationship.