BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing

Am J Obstet Gynecol. 1998 Apr;178(4):670-7. doi: 10.1016/s0002-9378(98)70476-4.


Objective: Our purpose was to determine the prevalence of BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in a large, unselected population of ovarian cancer patients and to evaluate the relationship between mutation status and a routinely obtained family history of cancer.

Study design: One hundred sixteen consecutive ovarian cancer patients seen for routine clinical care were examined for BRCA1, BRCA2, hMSH2, and hMLH1 gene mutations with use of the polymerase chain reaction, single-strand conformation polymorphism analysis, and direct gene sequencing. Fisher's exact test was used to evaluate possible associations between BRCA1 and BRCA2 mutation status and specific familial characteristics.

Results: Among 116 unselected ovarian cancer patients we identified a total of 13 germline mutations in 12 patients: 10 in BRCA1, one each in hMSH2 and hMLH1, and a single BRCA2 mutation, which occurred in a patient also carrying a BRCA1 mutation. More than half the patients with BRCA1 mutations had family histories that would generally be considered unremarkable. Of 22 family history variables analyzed, only two (maternal family history of breast or ovarian cancer, p=0.037, and maternal family history of any cancer, p=0.020) conferred a significantly increased risk of carrying a BRCA1 mutation compared with ovarian cancer patients without such a history. However, the majority of ovarian cancer patients with these family histories and other suggestive histories tested negative for mutations.

Conclusions: Approximately 10% of ovarian cancers occur in association with genetic mutations known to predispose to the disease. A routinely obtained family history is an unreliable way to identify patients who might harbor mutations. The majority of ovarian cancer patients with suggestive family histories test negative for known gene mutations, perhaps suggesting the existence of additional undiscovered genes predisposing to ovarian cancer.

MeSH terms

  • Adult
  • BRCA2 Protein
  • Breast Neoplasms / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Female
  • Genes, BRCA1 / genetics*
  • Humans
  • Middle Aged
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Ovarian Neoplasms / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Sequence Analysis, DNA
  • Transcription Factors / genetics*


  • BRCA2 Protein
  • Neoplasm Proteins
  • Transcription Factors