title: Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years.
abstract: Although well studied in families at high-risk, the roles of mutations in the BRCA1 and BRCA2 genes are poorly understood in breast cancers in the general population, particularly in Black women and in age groups outside of the very young. We examined the prevalence and predictors of BRCA1 and BRCA2 mutations in 1,628 women with breast cancer and 674 women without breast cancer who participated in a multicenter population-based case-control study of Black and White women, 35 to 64 years of age. Among cases, 2.4% and 2.3% carried deleterious mutations in BRCA1 and BRCA2, respectively. BRCA1 mutations were significantly more common in White (2.9%) versus Black (1.4%) cases and in Jewish (10.2%) versus non-Jewish (2.0%) cases; BRCA2 mutations were slightly more frequent in Black (2.6%) versus White (2.1%) cases. Numerous familial and demographic factors were significantly associated with BRCA1 and, to a lesser extent, BRCA2 carrier status, when examined individually. In models considering all predictors together, early onset ages in cases and in relatives, family history of ovarian cancer, and Jewish ancestry remained strongly and significantly predictive of BRCA1 carrier status, whereas BRCA2 predictors were fewer and more modest in magnitude. Both the combinations of predictors and effect sizes varied across racial/ethnic and age groups. These results provide first-time prevalence estimates for BRCA1/BRCA2 in breast cancer cases among understudied racial and age groups and show key predictors of mutation carrier status for both White and Black women and women of a wide age spectrum with breast cancer in the general population.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. kmalone@fhcrc.org
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Malone
authors.forename: Janet R
authors.initials: JR
authors.lastname: Daling
authors.forename: David R
authors.initials: DR
authors.lastname: Doody
authors.forename: Li
authors.initials: L
authors.lastname: Hsu
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Coates
authors.forename: Polly A
authors.initials: PA
authors.lastname: Marchbanks
authors.forename: Michael S
authors.initials: MS
authors.lastname: Simon
authors.forename: Jill A
authors.initials: JA
authors.lastname: McDonald
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Norman
authors.forename: Brian L
authors.initials: BL
authors.lastname: Strom
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Burkman
authors.forename: Giske
authors.initials: G
authors.lastname: Ursin
authors.forename: Dennis
authors.initials: D
authors.lastname: Deapen
authors.forename: Linda K
authors.initials: LK
authors.lastname: Weiss
authors.forename: Suzanne
authors.initials: S
authors.lastname: Folger
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Madeoy
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Friedrichsen
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Suter
authors.forename: Mariela C
authors.initials: MC
authors.lastname: Humphrey
authors.forename: Robert
authors.initials: R
authors.lastname: Spirtas
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D044383:Black People / Q000706:statistics & numerical data*; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D014481:United States; D044465:White People / Q000706:statistics & numerical data*; D001741:Black or African American
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein