BRCA Mutations Increase Fertility in Families at Hereditary Breast/Ovarian Cancer Risk

<div><p>Background</p><p>Deleterious mutations in the BRCA genes are responsible for a small, but significant, proportion of breast and ovarian cancers (5 - 10 %). Proof of <i>de novo</i> mutations in hereditary breast/ovarian cancer (HBOC) families is rare, in contrast to founder mutations, thousands of years old, that may be carried by as much as 1 % of a population. Thus, if mutations favoring cancer survive selection pressure through time, they must provide advantages that compensate for the loss of life expectancy.</p><p>Method</p><p>This hypothesis was tested within 2,150 HBOC families encompassing 96,325 individuals. Parameters included counts of breast/ovarian cancer, age at diagnosis, male breast cancer and other cancer locations. As expected, well-known clinical parameters discriminated between BRCA-mutated families and others: young age at breast cancer, ovarian cancer, pancreatic cancer and male breast cancer. The major fertility differences concerned men in BRCA-mutated families: they had lower first and mean age at paternity, and fewer remained childless. For women in BRCA families, the miscarriage rate was lower. In a logistic regression including clinical factors, the different miscarriage rate and men's mean age at paternity remained significant.</p><p>Results</p><p>Fertility advantages were confirmed in a subgroup of 746 BRCA mutation carriers and 483 non-carriers from BRCA mutated families. In particular, female carriers were less often nulliparous (9.1 % of carriers versus 16.0 %, p = 0.003) and had more children (1.8 ± 1.4 SD versus 1.5 ± 1.3, p = 0.002) as well as male carriers (1.7 ± 1.3 versus 1.4 ± 1.3, p = 0.024).</p><p>Conclusion</p><p>Although BRCA mutations shorten the reproductive period due to cancer mortality, they compensate by improving fertility both in male and female carriers.</p></div

Cancer locations predicting the BRCA mutational risk.

<p>(logistic regression: p-values complete the information given by each Odds-Ratio; error bars represent 95%-CI of Odds-Ratios; covariates are cancer locations and "Breast < 30" means female breast cancers occurring before 30 years…).</p

Accrual flowchart of the families and the individuals selected from the Database.

<p>Accrual flowchart of the families and the individuals selected from the Database.</p

Additional file 1: of BRACAVENIR - impact of a psychoeducational intervention on expectations and coping in young women (aged 18–30 years) exposed to a high familial breast/ovarian cancer risk: study protocol for a randomized controlled trial

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 checklist. (DOC 120 kb