Genes Related to Diabetes May Be Associated With Pancreatic Cancer in a Population-Based Case-Control Study in Minnesota

Objectives: Type 2 diabetes is associated with increased pancreatic cancer risk; however, the nature of this relationship is not clear. We examined the link between 10 diabetes-related single-nucleotide polymorphisms and pancreatic cancer in a case-control study conducted in 1994 to 1998. Methods: Cases (n = 162) were ascertained from hospitals in the Twin Cities and Mayo Clinic, Minn. Controls (n = 540) from the general population were frequency matched by age, sex, and race. Unconditional logistic regression provided odds ratios of pancreatic cancer and 95% confidence intervals (95% CIs). Results: In a multivariate-adjusted model, a significant association was observed only for rs780094 in the glucokinase regulator (GCKR) gene: odds ratios for pancreatic cancer were 1.00 for TT, 1.35 (95% CI, 0.71-2.58) for CT, and 2.14 (95% CI, 1.12-4.08) for CC genotypes (P trend = 0.01) and did not change after the adjustment for diabetes. Conclusions: This study provides the first evidence that GCKR rs780094, a single-nucleotide polymorphism related to diabetes, may be associated with pancreatic cancer risk. Although the results from this analysis are preliminary, there is a biologic plausibility for such an association.