Gynecologic surgeries and risk of ovarian cancer in carriers and non-carriers of the BRCA1 and BRCA2 ashkenazi founder mutations

PURPOSE: Case-control and cohort studies have established that gynecologic surgeries reduce the risk of developing ovarian cancer. It is not clear whether these surgeries also reduce risk in BRCA1 and BRCA2 mutation carriers. We studied Jewish women with incident ovarian cancer and tested for an Ashkenazi founder mutation (185 delAG and 5382insC in BRCA1 and/or 6174delT in BRCA2) to assess risk of ovarian cancer following gynecologic surgery. METHODS: Cases were identified in a population-based case-control study between 1994 and 1999. Controls were selected from the Central Population Registry and were matched to the cases based on age (within 2 years), area of birth, and place and length of residence in Israel. Excluding subjects reporting a bilateral oophorectomy, we tested 840 cases and 751 controls for the founder mutations. There were 244 (29%) cases that tested positive for BRCA1 and BRCA2, and 13 (1.7%) controls that tested positive. We used conditional logistic regression to estimate odds ratios (ORs) for developing ovarian cancer following selected gynecologic surgeries. RESULTS: Overall, gynecologic surgeries reduced the risk of ovarian cancer by 45% compared to women never having a gynecologic surgery (odds ratio (OR) = 0.55, 95% Confidence Interval (95% CI) = 0.44–0.70) after adjusting for age, ethnicity, parity, and oral contraceptive use. The risk estimate for BRCA1 and BRCA2 mutation carriers with a gynecologic surgery compared to the controls was also protective (OR = 0.51, 95% CI = 0.32–0.81). CONCLUSION: Israeli women who are carriers or non-carriers of mutations in BRCA1 and/or BRCA2 appear to benefit from a reduced risk of ovarian cancer following a gynecologic surgery.