title: Increased cancer risks for relatives of very early-onset breast cancer cases with and without BRCA1 and BRCA2 mutations.
abstract: BACKGROUND
  Little is known regarding cancer risks for relatives of women with very early-onset breast cancer.
  
  
  METHODS
  We studied 2208 parents and siblings of 504 unselected population-based Caucasian women with breast cancer diagnosed before age 35 years (103 from USA, 124 from Canada and 277 from Australia), 41 known to carry a mutation (24 in BRCA1, 16 in BRCA2 and one in both genes). Cancer-specific standardised incidence ratios (SIRs) were estimated by comparing the number of affected relatives (50% verified overall) with that expected based on incidences specific for country, sex, age and year of birth.
  
  
  RESULTS
  For relatives of carriers, the female breast cancer SIRs were 13.13 (95% CI 6.57-26.26) and 12.52 (5.21-30.07) for BRCA1 and BRCA2, respectively. The ovarian cancer SIR was 12.38 (3.1-49.51) for BRCA1 and the prostate cancer SIR was 18.55 (4.64-74.17) for BRCA2. For relatives of non-carriers, the SIRs for female breast, prostate, lung, brain and urinary cancers were 4.03 (2.91-5.93), 5.25 (2.50-11.01), 7.73 (4.74-12.62), 5.19 (2.33-11.54) and 4.35 (1.81-10.46), respectively. For non-carriers, the SIRs remained elevated and were statistically significant for breast and prostate cancer when based on verified cancers.
  
  
  CONCLUSIONS
  First-degree relatives of women with very early-onset breast cancer are at increased risk of cancers not explained by BRCA1 and BRCA2 mutations.
authors.affiliation: Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Level 1, 723 Swanston Street, Melbourne, Carlton VIC 3053, Australia.
authors.forename: G S
authors.initials: GS
authors.lastname: Dite
authors.forename: A S
authors.initials: AS
authors.lastname: Whittemore
authors.forename: J A
authors.initials: JA
authors.lastname: Knight
authors.forename: E M
authors.initials: EM
authors.lastname: John
authors.forename: R L
authors.initials: RL
authors.lastname: Milne
authors.forename: I L
authors.initials: IL
authors.lastname: Andrulis
authors.forename: M C
authors.initials: MC
authors.lastname: Southey
authors.forename: M R E
authors.initials: MR
authors.lastname: McCredie
authors.forename: G G
authors.initials: GG
authors.lastname: Giles
authors.forename: A
authors.initials: A
authors.lastname: Miron
authors.forename: A I
authors.initials: AI
authors.lastname: Phipps
authors.forename: D W
authors.initials: DW
authors.lastname: West
authors.forename: J L
authors.initials: JL
authors.lastname: Hopper
mesh_terms: D000328:Adult; D017668:Age of Onset; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005190:Family; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D009035:Mothers; D009154:Mutation; D012306:Risk; D035781:Siblings