title: Family history of cancer and cancer risks in women with BRCA1 or BRCA2 mutations.
abstract: Women who carry a deleterious mutation in BRCA1 or BRCA2 have high lifetime risks of breast and ovarian cancers. However, the influence of a family history of these cancers on these risks in women with BRCA mutations is unclear. We calculated cancer incidence rates for a multinational cohort comprising 3011 women with BRCA1 or BRCA2 mutations who were followed up for a mean of 3.9 years, during which time 243 incident breast or ovarian cancers were recorded. The 10-year cumulative risks of breast cancer were 18.1% (95% confidence interval [CI] = 13.3% to 22.8%) for women with a BRCA1 mutation and 15.2% (95% CI = 9.1% to 21.2%) for women with a BRCA2 mutation. Among women with a BRCA1 mutation, the risk of breast cancer increased by 1.2-fold for each first-degree relative with breast cancer before age 50 years (hazard ratio [HR] = 1.21; 95% confidence interval [CI] = 0.94 to 1.57) and the risk of ovarian cancer increased by 1.6 fold for each first- or second-degree relative with ovarian cancer (HR = 1.61; 95% CI = 1.21 to 2.14). Among women with a BRCA2 mutation, the risk of breast cancer increased by 1.7-fold for each first-degree relative younger than 50 years with breast cancer (HR = 1.67; 95% CI = 1.04 to 2.07).
authors.affiliation: Women's College Research Institute, Toronto, ON, Canada.
authors.forename: Kelly
authors.initials: K
authors.lastname: Metcalfe
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Parviz
authors.initials: P
authors.lastname: Ghadirian
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: Charmaine
authors.initials: C
authors.lastname: Kim-Sing
authors.forename: Susan
authors.initials: S
authors.lastname: Neuhausen
authors.forename: Nadine
authors.initials: N
authors.lastname: Tung
authors.forename: Barry
authors.initials: B
authors.lastname: Rosen
authors.forename: Jacek
authors.initials: J
authors.lastname: Gronwald
authors.forename: Peter
authors.initials: P
authors.lastname: Ainsworth
authors.forename: Kevin
authors.initials: K
authors.lastname: Sweet
authors.forename: Andrea
authors.initials: A
authors.lastname: Eisen
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human