title: Cancer risks in first degree relatives of BRCA1 mutation carriers: effects of mutation and proband disease status.
abstract: BACKGROUND
  Mutations in the BRCA1 (MIM 113705) gene are found in many families with multiple cases of breast and ovarian cancer, and women with a BRCA1 mutation are at significantly higher risk of developing breast and ovarian cancer than are the general public.
  
  
  METHODS
  We obtained blood samples and pedigree information from 3568 unselected cases of early-onset breast cancer and 609 unselected patients with ovarian cancer from hospitals throughout Poland. Genetic testing was performed for three founder BRCA1 mutations. We also calculated the risk of breast and ovarian cancer to age 75 in the first degree relatives of carriers using Kaplan-Meier methods.
  
  
  RESULTS
  The three founder BRCA1 mutations were identified in 273 samples (187 with 5382insC, 22 with 4153delA, and 64 with C61G). A mutation was present in 4.3% of patients with breast cancer and 12.3% of patients with ovarian cancer. The overall risk of breast cancer to age 75 in relatives was 33% and the risk of ovarian cancer was 15%. The risk for breast cancer was 42% higher among first degree relatives of carriers of the C61G missense mutation compared to other mutations (HR = 1.42; p = 0.10) and the risk for ovarian cancer was lower than average (OR = 0.26; p = 0.03). Relatives of women diagnosed with breast cancer had a higher risk of breast cancer than relatives of women diagnosed with ovarian cancer (OR = 1.7; p = 0.03).
  
  
  CONCLUSIONS
  The risk of breast cancer in female relatives of women with a BRCA1 mutation depends on whether the proband was diagnosed with breast or ovarian cancer.
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Gronwald
authors.forename: T
authors.initials: T
authors.lastname: Huzarski
authors.forename: B
authors.initials: B
authors.lastname: Byrski
authors.forename: K
authors.initials: K
authors.lastname: Medrek
authors.forename: J
authors.initials: J
authors.lastname: Menkiszak
authors.forename: A N
authors.initials: AN
authors.lastname: Monteiro
authors.forename: P
authors.initials: P
authors.lastname: Sun
authors.forename: J
authors.initials: J
authors.lastname: Lubinski
authors.forename: S A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D012307:Risk Factors