Type 2 Diabetes Susceptibility Variants Contribute to Breast Cancer Risk
Variants associated with type 2 diabetes (T2D) have been previously examined for association with breast cancer, but nearly all were intronic or intergenic. Our rich AmbryShare phenotype and exome sequence data afforded us an opportunity to examine the association between 21 T2D coding variants and breast cancer.
Among Caucasian breast cancer patients and controls, we identified four variants associated with breast cancer in genes ASCC2, PPARG, PAM, and PPIPK52. The strongest of these signals was PPARG P12A (additive model OR=1.63, p=1 x 10^-21).
Association between breast cancer and PPARG P12A was also observed in Hispanics and South Asians, and consistently significant in analyses of pathology-specific subtypes, with slightly stronger association with TPBC and TNBC.
Results also consistently held up in sensitivity analyses of females only, and among those not carrying mutations in other major cancer-causing genes.
PPARG P12A and other T2D-related variants may confer a moderate level of risk for breast cancer, and could have an important role in breast cancer etiology particularly when no high penetrance mutations are present.
Authors: Mary Helen Black; Shuwei Li; Brice Sarver; Aaron Elliott; Hsiao-Mei Lu