title: BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases.
abstract: BACKGROUND
  It is believed that BRCA1 and BRCA2 germline mutations account for the majority of hereditary ovarian carcinomas; however, to the authors' knowledge, there are scant data on the prevalence and spectrum of mutations, genotype/phenotype correlations, tumor histology, and family history characteristics. To address this gap, the authors conducted a population-based study of 232 incident epithelial ovarian carcinomas in the Tampa Bay area.
  
  
  METHODS
  Genetic testing for the BRCA1 and BRCA2 genes was performed through full sequencing and BRCA1 rearrangement testing.
  
  
  RESULTS
  Of 209 women with invasive ovarian carcinoma, 32 women (15.3%) had mutations in BRCA1 or BRCA2, including 20 BRCA1 mutations and 12 BRCA2 mutations. Of the BRCA2 mutations, 58% were outside the "ovarian cancer cluster region" (OCCR). Variants of uncertain significance were detected in 8.2% of women with invasive ovarian carcinoma. No mutations were identified in women with borderline or invasive mucinous tumors. Among the BRCA mutation-positive women, 63% had serous tumors. A family history of breast and/or ovarian carcinoma was reported in 65%, 75%, and 43.5% of relatives of BRCA1 carriers, BRCA2 carriers, and non-BRCA1/BRCA2 carriers, respectively.
  
  
  CONCLUSIONS
  The data from this study suggested that 1) previous studies may have underestimated the frequency of BRCA1 and BRCA2 mutations in ovarian carcinomas, especially outside the OCCR; 2) it may be reasonable to offer genetic counseling to any woman with an invasive, nonmucinous epithelial ovarian tumor; and 3) among patients with invasive ovarian carcinoma, family history is not sufficiently accurate to predict mutation status.
authors.affiliation: Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33617, USA.
authors.forename: Tuya
authors.initials: T
authors.lastname: Pal
authors.forename: Jenny
authors.initials: J
authors.lastname: Permuth-Wey
authors.forename: Judith A
authors.initials: JA
authors.lastname: Betts
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Krischer
authors.forename: James
authors.initials: J
authors.lastname: Fiorica
authors.forename: Hector
authors.initials: H
authors.lastname: Arango
authors.forename: James
authors.initials: J
authors.lastname: LaPolla
authors.forename: Mitchell
authors.initials: M
authors.lastname: Hoffman
authors.forename: Martin A
authors.initials: MA
authors.lastname: Martino
authors.forename: Katie
authors.initials: K
authors.lastname: Wakeley
authors.forename: George
authors.initials: G
authors.lastname: Wilbanks
authors.forename: Santo
authors.initials: S
authors.lastname: Nicosia
authors.forename: Alan
authors.initials: A
authors.lastname: Cantor
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sutphen
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D011336:Probability; D011379:Prognosis; D018570:Risk Assessment; D015996:Survival Rate