title: Central European BRCA2 mutation carriers: birth cohort status correlates with onset of breast cancer.
abstract: BACKGROUND
  Mutations in brca1 and 2 genes lead to a significant increase in the lifetime risk of developing breast (BC) and ovarian cancer (OC). There are indications that birth cohort can influence the cancer risk in brca1 mutation carriers. Therefore, we investigated the risks for BC and OC associated with brca2 mutations in a cohort of female mutation carriers of a genetically heterogeneous Central European population.
  
  
  METHODS
  This study included 246 women in whom a functional mutation in the brca2 gene had been identified at our institution. At the time of analysis, 153 women had developed cancer (142 BC, 9 OC, 2 BC and OC). Risks were estimated using the product limit method. The log rank test was used to compare different strata.
  
  
  RESULTS
  After correction for risk-reducing surgeries, the cumulative risk of developing cancer to age 70 was found to be 88% for BC (95% CI 81-95%) and 31% for OC (95% CI 17-45%). Female brca2 mutation carriers born in 1958 or later were at a significantly higher risk of developing BC at a younger age (p<0.001), while no such age cohort-dependent correlation was found for OC.
  
  
  CONCLUSIONS
  The age cohort-dependent early onset in BC in women born after 1958 strongly suggests the importance of exogenous factors such as lifestyle modification while this does not seem to be the case for OC. Female brca2 mutation carriers should be counseled about their age cohort-dependent breast cancer risk.
authors.affiliation: Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. Electronic address: muy-kheng.tea@meduniwien.ac.at.
authors.forename: Muy-Kheng M
authors.initials: MK
authors.lastname: Tea
authors.affiliation: Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Kaiser Franz Josef Hospital, SMZ-Süd, Department of OB/GYN, Vienna, Austria.
authors.forename: Regina
authors.initials: R
authors.lastname: Kroiss
authors.affiliation: Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Muhr
authors.affiliation: Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Fuerhauser-Rappaport
authors.affiliation: University of Regensburg, Institute of Functional Genomics, Regensburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Oefner
authors.affiliation: Kaiser Franz Josef Hospital, SMZ-Süd, Department of OB/GYN, Vienna, Austria.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Wagner
authors.affiliation: Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D015331:Cohort Studies; D005060:Europe; D005260:Female; D024522:Genes, BRCA2; D014644:Genetic Variation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D012306:Risk; D055815:Young Adult
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA2; Breast cancer risk; Hereditary breast and ovarian cancer; Penetrance of BRCA2