title: Cancer risks in carriers of the BRCA1/2 Ashkenazi founder mutations.
abstract: BACKGROUND
  The risks for cancers other than breast (BC) or ovarian (OC) cancer in breast cancer gene 1 and 2 (BRCA1/2) mutation carriers were elevated in studies of carrier families. However, case-control studies did not confirm this observation.
  
  
  OBJECTIVE
  To compare the risks for other cancers in BRCA1/2 mutation carriers and non-carriers, all affected with BC and/or OC. Both groups share risk modifiers of BC/OC, which enabled assessment of the role of BRCA1/2 mutations.
  
  
  METHODS
  1098 Ashkenazi Jewish women affected with BC and/or OC were ascertained during 1995-2003; molecular testing revealed 229 BRCA1 and 100 BRCA2 carriers and 769 non-carriers. COX proportional hazard models were used to evaluate the risk of other cancers. Analyses were conducted including all other cancers or only those diagnosed after BC/OC diagnosis.
  
  
  RESULTS
  The HRs for any other cancer were 2.6 (95% CI 1.7 to 4.2, p<0.001) and 1.8 (95% CI 0.95 to 3.6, p = 0.07) in BRCA1 and BRCA2 carriers, respectively. The corresponding colon cancer HRs were 3.9 (95% CI 1.3 to 12.1, p = 0.02) and 2.3 (95% CI 0.5 to 11.3, p = 0.3) in BRCA1 and BRCA2 carriers. The HR for lymphoma was 11.9 (95% CI 3.1 to 46.2, p = 0.001) in BRCA2 carriers. Risk estimates for other cancers after the onset of BC/OC were similar.
  
  
  CONCLUSIONS
  A 2.5-fold increase in any other cancer and a fourfold risk of colon cancer were found among BRCA1 carriers. The corresponding HRs in BRCA2 carriers were non-significant, except for the markedly elevated risk of lymphoma. These results suggest a role for BRCA1/2 mutations in colorectal cancer risk in a subgroup of BC/OC-affected carriers.
authors.forename: Luna
authors.initials: L
authors.lastname: Kadouri
authors.forename: Ayala
authors.initials: A
authors.lastname: Hubert
authors.forename: Yakir
authors.initials: Y
authors.lastname: Rotenberg
authors.forename: Tamar
authors.initials: T
authors.lastname: Hamburger
authors.forename: Michal
authors.initials: M
authors.lastname: Sagi
authors.forename: Chovav
authors.initials: C
authors.lastname: Nechushtan
authors.forename: Dvorah
authors.initials: D
authors.lastname: Abeliovich
authors.forename: Tamar
authors.initials: T
authors.lastname: Peretz
mesh_terms: D001943:Breast Neoplasms / Q000150:complications / Q000235:genetics*; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007585:Jews; D008223:Lymphoma / Q000209:etiology / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000150:complications / Q000235:genetics*; D016016:Proportional Hazards Models; D018570:Risk Assessment