Association study of type 2 diabetes genetic susceptibility variants and risk of pancreatic cancer: an analysis of PanScan-I data

To examine associations between recently identified common type 2 diabetes (T2D) susceptibility genetic variants and pancreatic cancer risk. Using data on individuals of European ancestry from the Cancer Genetic Markers of Susceptibility PanScan-I study (1,763 pancreatic cancer cases and 1,802 controls), we tested associations for 37 T2D susceptibility variants with pancreatic cancer risk. Associations with pancreatic cancer were also tested for three composite T2D susceptibility measures, incorporating data on all 37 variants, and for ten additional variants related to T2D-related phenotypes, including fasting glucose and beta-cell function. Of the 37 T2D risk alleles, two showed nominally significant positive associations with pancreatic cancer risk (FTO rs8050136 per-allele OR = 1.12; CI: 1.02-1.23; MTNR1B rs1387153 OR = 1.11; CI: 1.00-1.23) and one showed an inverse association (BCL11A rs243021 OR = 0.88; CI: 0.80-0.97). The composite T2D susceptibility measures were not associated with pancreatic cancer. The glucose-raising allele of MADD rs11039149 was associated with increased risk of pancreatic cancer (OR = 1.14; CI: 1.03-1.27). Overall, these results do not provide strong evidence that common variants underling T2D or related phenotypes also affect pancreatic cancer risk; however, associations for FTO, MTNR1B, BCL11A, and MADD variants warrant further investigation in larger studies. Hypothesis-driven analyses of existing genome-wide genetic data can be cost-efficient and promising approaches for investigating genetic susceptibility to complex diseases.