Effects of BRCA1 and BRCA2 mutations on female fertility

Department of Family and Consumer Studies, University of Utah, 225 South 1400 East Alfred Emery Building 228, Salt Lake City, UT 84112, USA.
Proceedings of the Royal Society B: Biological Sciences (Impact Factor: 5.05). 04/2012; 279(1732):1389-95. DOI: 10.1098/rspb.2011.1697
Source: PubMed


Women with BRCA1/2 mutations have a significantly higher lifetime risk of developing breast or ovarian cancer. We suggest that female mutation carriers may have improved fitness owing to enhanced fertility relative to non-carriers. Here we show that women who are carriers of BRCA1/2 mutations living in natural fertility conditions have excess fertility as well as excess post-reproductive mortality in relation to controls. Individuals who tested positive for BRCA1/2 mutations who linked into multi-generational pedigrees within the Utah Population Database were used to identify putative obligate carriers. We find that women born before 1930 who are mutation carriers have significantly more children than controls and have excess post-reproductive mortality risks. They also have shorter birth intervals and end child-bearing later than controls. For contemporary women tested directly for BRCA1/2 mutations, an era when modern contraceptives are available, differences in fertility and mortality persist but are attenuated. Our findings suggest the need to re-examine the wider role played by BRCA1/2 mutations. Elevated fertility of female mutation carriers indicates that they are more fecund despite their elevated post-reproductive mortality risks.

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    • "The two studies that looked at the parity were questionnaire studies, which also did not have the numbers to address age stratification[57,58]. Interestingly, one study claimed increased fertility in women with BRCA mutations[59]. However, the study was hampered by retrospective design; absence of information on confounding factors, such as smoking and oral contraceptive use; and heterogeneous control (including untested women) and study (including both affected and unaffected carriers and no differentiation of BRCA1 vs. BRCA2 mutations) groups. "
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