Effects of BRCA1 and BRCA2 Mutations on Fertility and Later-Life Survival

Ken R. Smith, University of Utah
Heidi Hanson, Huntsman Cancer Institute
Geraldine P. Mineau, University of Utah
Saundra Buys, Huntsman Cancer Institute

The purpose of this study is to address three questions. First, from an evolutionary standpoint, what mechanisms might explain why BRCA1 and BRCA2 mutations persist in human populations given their adverse health consequences effects? Second, how has fertility behavior changed with the advent of genetic testing where individuals may now make family planning decisions based on a family cancer history or predictive genetic risk information heretofore unavailable? What is the mortality consequence of being a BRCA1/2 mutation carrier? We use the Utah Population Database linked to two large samples where BRCA1/2 mutation status is known; we have identified 177 putative obligate carriers and 449 tested carriers as well as 200,000 matched controls. We find that female mutation carriers have excess fertility and post-menopausal mortality; there is also support for a shrinking influence of carrier status over time.