title: Variation of breast cancer risk among BRCA1/2 carriers.
abstract: BACKGROUND
  The risk of breast cancer in BRCA1 and BRCA2 mutation carriers has been examined in many studies, but relatively little attention has been paid to the degree to which the risk may vary among carriers.
  
  
  OBJECTIVE
  To determine the extent to which risks for BRCA1 and BRCA2 carriers vary with respect to observable and unobservable characteristics.
  
  
  METHODS
  Probands were identified from a population-based, case-control study (Women's Environmental Cancer and Radiation Epidemiology [WECARE]) of asynchronous contralateral breast cancer conducted during the period of January 2000 to July 2004. Participants previously diagnosed with contralateral breast cancer or unilateral breast cancer were genotyped for mutations in BRCA1 and BRCA2. All participants had their initial breast cancer diagnosed during the period of January 1985 to December 2000, before the age of 55 years.
  
  
  METHODS
  Incidence of breast cancer in first-degree female relatives of the probands was examined and compared on the basis of proband characteristics and on the basis of variation between families.
  
  
  RESULTS
  Among the 1394 participants with unilateral breast cancer, 73 (5.2%) were identified as carriers of deleterious mutations (42 with BRCA1 and 31 with BRCA2). Among the 704 participants with contralateral breast cancer, 108 (15.3%) were identified as carriers of deleterious mutations (67 with BRCA1 and 41 with BRCA2). Among relatives of carriers, risk was significantly associated with younger age at diagnosis in the proband (P = .04), and there was a trend toward higher risk for relatives of contralateral breast cancer vs unilateral breast cancer participants (odds ratio, 1.4 [95% confidence interval, 0.8-2.4]; P = .28). In addition, there were significant differences in risk between carrier families after adjusting for these observed characteristics.
  
  
  CONCLUSIONS
  There exists broad variation in breast cancer risk among carriers of BRCA1 and BRCA2 mutations.
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. beggc@mskcc.org
authors.forename: Colin B
authors.initials: CB
authors.lastname: Begg
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Malone
authors.forename: Patrick
authors.initials: P
authors.lastname: Concannon
authors.forename: Duncan C
authors.initials: DC
authors.lastname: Thomas
authors.forename: Bryan
authors.initials: B
authors.lastname: Langholz
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Jørgen H
authors.initials: JH
authors.lastname: Olsen
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.forename: Hoda
authors.initials: H
authors.lastname: Anton-Culver
authors.forename: Marinela
authors.initials: M
authors.lastname: Capanu
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liang
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Hummer
authors.forename: Cami
authors.initials: C
authors.lastname: Sima
authors.forename: Jonine L
authors.initials: JL
authors.lastname: Bernstein
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009154:Mutation; D012306:Risk