Impact of BRCA mutations on female fertility and offspring sex ratio

Authors

  • Roxana Moslehi,

    Corresponding author
    1. Department of Epidemiology and Biostatistics, School of Public Health, State University of New York at Albany, Rensselaer, New York 12144
    2. Center for Excellence in Cancer Genomics, State University of New York at Albany, Rensselaer, New York 12144
    • School of Public Health and Center for Excellence in Cancer Genomics, State University of New York (SUNY) at Albany, 1 Discovery Drive, Room 310, Rensselaer, NY 12144, USA
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  • Ranjana Singh,

    1. Department of Epidemiology and Biostatistics, School of Public Health, State University of New York at Albany, Rensselaer, New York 12144
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  • Lawrence Lessner,

    1. Department of Epidemiology and Biostatistics, School of Public Health, State University of New York at Albany, Rensselaer, New York 12144
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  • Jan M. Friedman

    1. Department of Medical Genetics, University of British Columbia, Children's and Women's Hospital, Vancouver, British Columbia, Canada V6H 3N1
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  • There are no conflicts of interest for any of the authors on this manuscript.

Abstract

Positive selection for inherited mutations in breast and ovarian cancer predisposing genes, BRCA1 and BRCA2, may contribute to the high frequency of BRCA mutations among the Ashkenazi Jewish population. Impact of BRCA mutations on fertility has not been generally explored in epidemiologic studies. There are reports of distorted sex ratios in BRCA carrier families but these findings have been attributed to bias. We investigated the effect of BRCA mutations on female fertility and offspring sex ratio in a study of 260 Ashkenazi Jewish women with ovarian cancer and 331 controls, unselected for age or family history of the disease. Pregnancy success was similar for 96 mutation carrier (0.84) and 164 noncarrier cases (0.87) and controls (0.83). After adjusting for covariates, there were no significant differences between BRCA carrier and noncarrier cases and controls with regards to fertility, despite lower pregnancy rates among all cases compared to controls (P = 0.0049). Male/female sex ratios were significantly lower among offspring of carriers (0.71) than offspring of noncarriers (0.95) or those of the controls (0.99). Comparisons among the three groups yielded statistically significant distortion against males among the offspring of known and obligate BRCA carriers compared to noncarriers (OR = 0.74, 95% CI:0.55–0.99) and controls (OR = 0.71, 95% CI:0.54–0.94). In conclusion, we did not find evidence for an effect of BRCA mutations on female fertility. We found a significant excess of females among the offspring of female carriers of BRCA1 and BRCA2 mutations. Potential contribution of observed sex ratio distortions to positive selection for BRCA mutations may warrant further investigation. Am. J. Hum. Biol., 2010. © 2009 Wiley-Liss, Inc.

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