BRCA1 and BRCA2 Mutations Account for a Large Proportion of Ovarian Carcinoma Cases

Cancer. 2005 Dec 15;104(12):2807-16. doi: 10.1002/cncr.21536.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Age Distribution
  • Aged
  • Cohort Studies
  • Confidence Intervals
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Genetic Counseling
  • Genetic Predisposition to Disease / epidemiology*
  • Genetic Testing
  • Humans
  • Incidence
  • Middle Aged
  • Mutation*
  • Neoplasm Invasiveness / pathology*
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Pedigree
  • Probability
  • Prognosis
  • Risk Assessment
  • Survival Rate