The genetic epidemiology of early-onset epithelial ovarian cancer: a population-based study

Am J Hum Genet. 1999 Dec;65(6):1725-32. doi: 10.1086/302671.

Abstract

We conducted a population-based study to determine the contribution of germline mutations in known candidate genes to ovarian cancer diagnosed at age <30 years. Women with epithelial ovarian cancer were identified through cancer registries. DNA samples were analyzed for mutations in BRCA1, the "ovarian cancer-cluster region" (nucleotides 3139-7069) of BRCA2, and the mismatch-repair genes hMSH2 and hMLH1. Probable germline mutations in hMLH1 were identified in 2 (2%; 95% confidence interval 1%-8%) of 101 women with invasive ovarian cancer diagnosed at age <30 years. No germline mutations were identified in any of the other genes analyzed. There were no striking pedigrees suggestive of families with either breast/ovarian cancer or hereditary nonpolyposis colorectal cancer (HNPCC). There was a significantly increased incidence of all cancers in first-degree relatives of women with invasive disease (relative risk [RR] = 1.6, P=.01) but not in second-degree relatives or in relatives of women with borderline cases. First-degree relatives of women with invasive disease had increased risks of ovarian cancer (RR = 4.8, P=.03), myeloma (RR = 10, P=.01), and non-Hodgkin lymphoma (RR = 7, P=.004). Germline mutations in BRCA1, BRCA2, msh2, and mlh1 contribute to only a minority of cases of early-onset epithelial ovarian cancer. Our data suggest that early-onset ovarian cancer is not associated with a greatly increased risk of cancer in close relatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adolescent
  • Adult
  • Age of Onset
  • BRCA2 Protein
  • Carrier Proteins
  • Child
  • DNA Mutational Analysis*
  • DNA-Binding Proteins*
  • Family Health
  • Female
  • Genes, BRCA1 / genetics
  • Genetic Predisposition to Disease / genetics*
  • Germ-Line Mutation / genetics
  • Humans
  • Incidence
  • Male
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Neoplasm Proteins / genetics
  • Neoplasm, Residual / epidemiology
  • Neoplasm, Residual / genetics
  • Neoplasm, Residual / pathology
  • Neoplasms / epidemiology
  • Neoplasms / genetics
  • Nuclear Proteins
  • Odds Ratio
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / epidemiology*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Proto-Oncogene Proteins / genetics
  • Retrospective Studies
  • Survival Rate
  • Transcription Factors / genetics
  • United Kingdom / epidemiology

Substances

  • Adaptor Proteins, Signal Transducing
  • BRCA2 Protein
  • Carrier Proteins
  • DNA-Binding Proteins
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Transcription Factors
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein