Women who inherit mutations in BRCA1 or BRCA2 genes have a significant risk—as high as 80%—of getting breast cancer in their lifetimes, and a 40% to 60% risk of getting ovarian cancer. Perhaps worse, the children of these carriers have a 50% chance of inheriting the mutation.

“In the big scheme of evolution, harmful genes should have been eliminated from the human population over time,” says Huntsman Cancer Institute (HCI) investigator Ken Smith, PhD, professor in the Department of Family and Consumer Studies at the University of Utah and a member of HCIs Cancer Control and Population Sciences Program. “A gene that doesnt help people survive, reproduce, and rear their children to reach sexual maturity so they can reproduce will be removed from the population. So scientists have to ask, why do these BRCA mutations persist?”

The answer, says Smith, may lie in the fact that many genes have more than one function, and its possible for these multiple functions to work in opposite directions. From the standpoint of evolution, for a harmful mutation such as BRCA1/2 to be maintained in the population, there also could be some potential advantage to having it.

Smith, along with fellow HCI investigators and co-authors Geri Mineau, PhD, and Saundra Buys, MD, set out to examine the idea that increased fertility might be a potential advantage in BRCA mutations. Doctoral student Heidi Hanson was also a critical collaborator on the research team. Using information collected from the Utah Population Database (UPDB), they looked at patterns of both childbearing and early death in two groups of women with BRCA1/2 mutations representing two eras. They also looked at control groups who did not carry the mutation. One BRCA group consisted of women born before 1930, who would have completed their childbearing years before birth control was readily available and reliable. The other BRCA group was women from later generations who had access to effective birth control.  

“The UPDB made it possible for us to identify women known to be mutation carriers although they were not directly tested (obligate carriers) and examine information on their fertility before contraception was available,” says Smith. (Learn more about the UPDB in the 2011 HCI Annual Report.)

The researchers found that having a BRCA1/2 mutation enhances fertility. Women with the mutation who lived during a time when they did not have access to birth control had significantly more children than otherwise comparable women without the mutation. For BRCA1/2 carriers who lived when modern birth control methods were available, the fertility difference persists but it is not as large. At the same time, the study showed that in their post-reproductive years, more mutation carriers died at earlier ages than women lacking BRCA mutations. These results were published in Proceedings of the Royal Society, Biological Sciences.

“There arent many examples in the literature that show mutations being both harmful and beneficial, although it is often predicted,” Smith says. “We think this makes our result relatively novel—an argument explains why the BRCA mutations are still prevalent in the population.”

Interesting enough, but what does it mean for women who carry the BRCA mutation right now? “When women know or suspect they have an inherited predisposition for breast cancer, they may decide to limit the number of children they have,” says Smith. “According to our previous work, some women may not wish to pass on the risk to their children and hence they may forego having additional children. These women also may not want to put their children through the grief of seeing their mother suffer through breast cancer.”

Smith notes, “Genetic counselors can guide women concerned about known BRCA mutations toward the best family planning decisions for each individual.”

HCI's Family Cancer Assessment Clinic (FCAC) helps people with a considerable personal or family history of cancer find out whether genes play a role in their personal cancer risk. Learn more about the FCAC and genetic counseling.