Risk of endometrial carcinoma associated with BRCA mutation

Objective. Inherited mutations in the BRCA1 or BRCA2 genes are associated w ith a greatly increased lifetime risk of breast and ovarian cancers and a m odestly increased risk of several other cancer types. Several case reports of endometrial carcinoma in women with a BRCA mutation have led to speculat ion regarding the effect of these genes on the risk of endometrial cancer. The purpose of this study was to test the hypothesis that germline mutation of a BRCA gene is associated with an increased risk of endometrial carcino ma. Methods. A retrospective cohort of 199 consecutive Ashkenazi Jewish patient s with endometrial carcinoma was identified from a 12-year period at this i nstitution. All were genotyped for the three BRCA founder mutations (185del AG and 5382insC in BRCA1 and 6174delT in BRCA2) that exist in this populati on, and the case frequency was compared to the known population frequency o f these mutations. Additionally, endometrial carcinomas occurring in patien ts with BRCA mutations were assessed for somatic loss of the wild-type BRCA allele. Results. Germline BRCA mutations were identified in 3 (1 in BRCA1 and two i n BRCA2) of 199 (1.5%) patients, compared to a frequency of 2.0% in this po pulation generally. A relative risk of endometrial carcinoma associated wit h BRCA mutation, as estimated by the odds ratio, was calculated as 0.75 (95 % CI = 0.24-2.34; P = 0.6). Loss of the wild-type BRCA allele was observed in two of three tumors associated with a BRCA mutation, Conclusions. For individuals with a germline BRCA mutation, the lifetime ri sk of endometrial carcinoma is not increased, (C) 2001 Academic Press.