title: BRCA1 and BRCA2 mutation frequency in women evaluated in a breast cancer risk evaluation clinic.
abstract: OBJECTIVE
  To determine the prevalence of BRCA1 and BRCA2 mutations in families identified in a breast cancer risk evaluation clinic.
  
  
  METHODS
  One hundred sixty-four families seeking breast cancer risk evaluation were screened for coding region mutations in BRCA1 and BRCA2 by conformation-sensitive gel electrophoresis and DNA sequencing.
  
  
  RESULTS
  Mutations were identified in 37 families (22.6%); 28 (17.1%) had BRCA1 mutations and nine (5.5%) had BRCA2 mutations. The Ashkenazi Jewish founder mutations 185delAG and 5382insC (BRCA1) were found in 10 families (6.1%). However, 6174delT (BRCA2) was found in only one family (0.6%) despite estimates of equal frequency in the Ashkenazi population. In contrast to other series, the average age of breast cancer diagnosis was earlier in BRCA2 mutation carriers (32.1 years) than in women with BRCA1 mutations (37.6 years, P =.028). BRCA1 mutations were detected in 20 (45.5%) of 44 families with ovarian cancer and 12 (75%) of 16 families with both breast and ovarian cancer in a single individual. Significantly fewer BRCA2 mutations (two [4.5%] of 44) were detected in families with ovarian cancer (P =.01). Eight families had male breast cancer; one had a BRCA1 mutation and three had BRCA2 mutations.
  
  
  CONCLUSIONS
  BRCA1 mutations were three times more prevalent than BRCA2 mutations. Breast cancer diagnosis before 50 years of age, ovarian cancer, breast and ovarian cancer in a single individual, and male breast cancer were all significantly more common in families with BRCA1 and BRCA2 mutations, but none of these factors distinguished between BRCA1 and BRCA2 mutations. Evidence for reduced breast cancer penetrance associated with the BRCA2 mutation 6174delT was noted.
authors.affiliation: Abramson Family Cancer Research Institute and Department of Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Shih
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Couch
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Nathanson
authors.forename: M Anne
authors.initials: MA
authors.lastname: Blackwood
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
authors.forename: Katrina A
authors.initials: KA
authors.lastname: Armstrong
authors.forename: Kathleen
authors.initials: K
authors.lastname: Calzone
authors.forename: Jill
authors.initials: J
authors.lastname: Stopfer
authors.forename: Sheila
authors.initials: S
authors.lastname: Seal
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Weber
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D007585:Jews / Q000235:genetics; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics; D010375:Pedigree; D015995:Prevalence; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: D004273:DNA, Neoplasm