title: BRCA Mutations Increase Fertility in Families at Hereditary Breast/Ovarian Cancer Risk.
abstract: BACKGROUND
  Deleterious mutations in the BRCA genes are responsible for a small, but significant, proportion of breast and ovarian cancers (5 - 10 %). Proof of de novo 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Although BRCA mutations shorten the reproductive period due to cancer mortality, they compensate by improving fertility both in male and female carriers.
authors.affiliation: Centre Jean Perrin, Laboratoire d'Oncologie Moléculaire, 63011, Clermont-Ferrand, France; Université Blaise Pascal-Laboratoire de Mathématiques, UMR 6620-CNRS, Campus des Cézeaux-BP, 80026-63171, Aubière cedex, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Kwiatkowski
authors.affiliation: Centre Jean Perrin, Laboratoire d'Oncologie Moléculaire, 63011, Clermont-Ferrand, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Arbre
authors.affiliation: Université Clermont Auvergne, Université d'Auvergne, BP 10448, F-63000, Clermont-Ferrand, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Bidet
authors.affiliation: Centre Jean Perrin, Laboratoire d'Oncologie Moléculaire, 63011, Clermont-Ferrand, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Laquet
authors.affiliation: Centre Jean Perrin, Laboratoire d'Oncologie Moléculaire, 63011, Clermont-Ferrand, France.
authors.forename: Nancy
authors.initials: N
authors.lastname: Uhrhammer
authors.affiliation: Centre Jean Perrin, Laboratoire d'Oncologie Moléculaire, 63011, Clermont-Ferrand, France; Université Clermont Auvergne, Université d'Auvergne, BP 10448, F-63000, Clermont-Ferrand, France.
authors.forename: Yves-Jean
authors.initials: YJ
authors.lastname: Bignon
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D030541:Databases, Genetic; D005260:Female; D005298:Fertility / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D011110:Polymorphism, Genetic; D012372:ROC Curve; D012306:Risk
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human