Molecular genetics of hereditary ovarian cancer

Oncology (Williston Park). 1998 Mar;12(3):399-406; discussion 409-10, 413.

Abstract

Approximately 10% of all epithelial ovarian carcinoma cases are associated with inheritance of an autosomal-dominant genetic mutation conferring a predisposition to cancer with variable penetrance. Two such manifestations of hereditary ovarian cancer are currently recognized: the breast and ovarian cancer syndrome and the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. The breast and ovarian cancer syndrome is linked to the BRCA1 gene on chromosome 17q and, to a lesser extent, to the BRCA2 gene on chromosome 13q. The HNPCC syndrome is caused by any one of three known genes, hMSH2, hMLH1, and hPMS2, that encode proteins involved in the same pathway of DNA mismatch repair. Genetic screening for germ-line transmission of a defective allele of these genes is now possible for high-risk individuals. Despite the rapid pace of research advances in this area, however, considerable uncertainties remain regarding factors that affect the penetrance and tissue-specific expressivity of these mutations. Current research challenges include elucidating these modifying factors, gaining a better understanding of the biological function of BRCA1 and BRCA2 products, and determining the appropriate clinical intervention for genetically predisposed patients.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • BRCA1 Protein / genetics
  • BRCA2 Protein
  • Carrier Proteins
  • DNA Repair
  • DNA-Binding Proteins*
  • Female
  • Forecasting
  • Genetic Diseases, Inborn / genetics*
  • Humans
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Neoplasm Proteins / genetics
  • Nuclear Proteins
  • Ovarian Neoplasms / genetics*
  • Proto-Oncogene Proteins / genetics
  • Research
  • Risk Assessment
  • Transcription Factors / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • BRCA1 Protein
  • 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