title: Breast cancer risk for noncarriers of family-specific BRCA1 and BRCA2 mutations: findings from the Breast Cancer Family Registry.
abstract: OBJECTIVE
  Women with germline BRCA1 and BRCA2 mutations have five- to 20-fold increased risks of developing breast and ovarian cancer. A recent study claimed that women testing negative for their family-specific BRCA1 or BRCA2 mutation (noncarriers) have a five-fold increased risk of breast cancer. We estimated breast cancer risks for noncarriers by using a population-based sample of patients with breast cancer and their female first-degree relatives (FDRs).
  
  
  METHODS
  Patients were women with breast cancer and their FDRs enrolled in the population-based component of the Breast Cancer Family Registry; patients with breast cancer were tested for BRCA1 and BRCA2 mutations, as were FDRs of identified mutation carriers. We used segregation analysis to fit a model that accommodates familial correlation in breast cancer risk due to unobserved shared risk factors.
  
  
  RESULTS
  We studied 3,047 families; 160 had BRCA1 and 132 had BRCA2 mutations. There was no evidence of increased breast cancer risk for noncarriers of identified mutations compared with FDRs from families without BRCA1 or BRCA2 mutations: relative risk was 0.39 (95% CI, 0.04 to 3.81). Residual breast cancer correlation within families was strong, suggesting substantial risk heterogeneity in women without BRCA1 or BRCA2 mutations, with some 3.4% of them accounting for roughly one third of breast cancer cases.
  
  
  CONCLUSIONS
  These results support the practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA1 or BRCA2 mutation.
authors: Stanford University School of Medicine, Stanford, CA 94305, USA.
authors: Allison W
authors: AW
authors: Kurian
authors: Gail D
authors: GD
authors: Gong
authors: Esther M
authors: EM
authors: John
authors: David A
authors: DA
authors: Johnston
authors: Anna
authors: A
authors: Felberg
authors: Dee W
authors: DW
authors: West
authors: Alexander
authors: A
authors: Miron
authors: Irene L
authors: IL
authors: Andrulis
authors: John L
authors: JL
authors: Hopper
authors: Julia A
authors: JA
authors: Knight
authors: Hilmi
authors: H
authors: Ozcelik
authors: Gillian S
authors: GS
authors: Dite
authors: Carmel
authors: C
authors: Apicella
authors: Melissa C
authors: MC
authors: Southey
authors: Alice S
authors: AS
authors: Whittemore
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009154:Mutation; D012042:Registries; D012307:Risk Factors