Contribution of BRCA1 mutations to ovarian cancer

N Engl J Med. 1997 Apr 17;336(16):1125-30. doi: 10.1056/NEJM199704173361602.


Background: Inherited mutations in the BRCA1 gene confer a high risk of breast and ovarian cancer in some families. To determine the contribution of BRCA1 mutations to ovarian cancer in the general population, we analyzed DNA samples from a consecutive series of women with ovarian cancer seen at one center.

Methods: We studied 374 women who received a diagnosis of epithelial ovarian cancer before the age of 70 years and were treated at the Royal Marsden Hospital between July 1993 and September 1995. Genomic DNA was analyzed by multiplex heteroduplex analysis. Variants were further identified by sequencing.

Results: Probable germ-line BRCA1 mutations were identified in 13 of the 374 women (3 percent; 95 percent confidence interval, 2 to 6 percent). Six of the variants have not been described previously. Of the 13 mutations, 12 are predicted to result in a truncated protein product. An additional variant results in an in-frame deletion just outside the putative zinc-finger domain. Nine of the 12 women with truncating mutations had family histories of breast or ovarian cancer or both.

Conclusions: Assuming that our method has a sensitivity of 70 percent, mutations in BRCA1 occur in approximately 5 percent (95 percent confidence interval, 3 to 8 percent) of women in whom ovarian cancer is diagnosed before the age of 70 years.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / genetics
  • Adult
  • Aged
  • Cystadenocarcinoma / genetics*
  • DNA Mutational Analysis
  • Female
  • Genes, BRCA1*
  • Genetic Counseling
  • Germ-Line Mutation*
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / genetics*
  • Prevalence
  • Sensitivity and Specificity