Effects of BRCA Gene Mutations on Female Fertility and Offspring Sex Ratio

Roxana Moslehi, University at Albany, State University of New York (SUNY)
Ranjana Singh, University at Albany, State University of New York (SUNY)
Lawrence Lessner, University at Albany, State University of New York (SUNY)

In vitro and animal studies suggest an effect of inherited mutations in breast and ovarian cancer predisposing genes, BRCA1 and BRCA2, on fertility; however, no epidemiologic studies have been reported. There are reports of distorted sex ratios in BRCA carrier families but these findings remain equivocal. We investigated the effect of BRCA gene mutations on female fertility and offspring sex ratio using data from an ovarian cancer case-control study. Sex ratios among offspring of BRCA carrier cases were significantly distorted towards females as compared to non-carrier cases (OR=0.74, 95%CI: 0.55, 0.99) and controls (OR=0.72, 95%CI: 0.54, 0.94). Poisson distribution modeling of pregnancies among three groups, controlling for confounders such as oral contraceptive use, regularity of menstrual cycle, and body mass index showed lower fertility for BRCA mutation carriers compared to non-carriers; although the results did not reach statistical significance. Fertility was significantly lower for ovarian cancer cases compared to controls.