Novel breast cancer risk alleles and endometrial cancer risk.

Genome-wide association studies have identified several novel risk alleles for breast cancer. We hypothesized that genetic variants that are associated with breast cancer, a hormone-related disease, would also be associated with endometrial cancer, another hormone-related disease. We conducted a case-control study nested within the Nurses' Health Study and the Women's Health Study to investigate the associations between these 7 newly identified risk alleles for breast cancer and endometrial cancer risk using 692 invasive endometrial cancer cases and 1,723 matched controls. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the risk of endometrial cancer. In contrast to the breast cancer findings, we did not observe an increased risk of endometrial cancer. We observed an inverse association among rs2981582 (FGFR2) variant carriers [OR= 0.75 (95% CI: 0.60-0.95)]. We also observed a nonsignificant inverse association with rs889312 (MAP3K1) variant carriers [OR = 0.85 (95% CI: 0.68-1.05)] and rs1219648 (FGFR2) variant carriers [OR= 0.86 (95% CI: 0.69-1.06) and endometrial cancer risk. We did not observe associations with the other single nucleotide polymorphisms (SNPs) and endometrial cancer risk. Replication studies investigating these polymorphisms and endometrial cancer risk are warranted. However, our findings do suggest the potential importance of biological differences between endometrial and breast cancer with respect to the genes identified in the scans. The molecular mechanisms underlying these differences remain to be defined. (c) 2008 Wiley-Liss, Inc.