Ovarian cancer predisposition beyond BRCA1 and BRCA2 genes

Int J Gynecol Cancer. 2020 Nov;30(11):1803-1810. doi: 10.1136/ijgc-2020-001556. Epub 2020 Sep 6.

Abstract

Several genes associated with hereditary ovarian cancer have been discovered as a result of the work done with next generation sequencing. It is estimated that approximately 23% of ovarian carcinomas have a hereditary predisposition. The most common hereditary condition is represented by germline mutations in BRCA1 or BRCA2 genes that account for 20-25% of high grade serous ovarian cancer. A number of other hereditary ovarian cancers are associated with different genes, with a crucial role in the DNA damage response pathway, such as the mismatch repair genes in Lynch syndrome, TP53 in Li-Fraumeni syndrome, STK11 in Peutz-Jeghers syndrome, CHEK2, RAD51, BRIP1, and PALB2. The goal of this manuscript is to summarize the published data regarding the molecular pathways involved in the pathogenesis of non-BRCA related hereditary ovarian cancer and to provide a tool that might be useful in discussing risk assessment, genetic testing, prevention strategies, as well as clinical and therapeutic implications for patients with ovarian cancer.

Keywords: BRCA1 Protein; BRCA2 Protein; homologous recombination; ovarian cancer.

Publication types

  • Review

MeSH terms

  • BRCA1 Protein
  • BRCA2 Protein
  • Carcinoma, Ovarian Epithelial / genetics*
  • Carcinoma, Ovarian Epithelial / prevention & control
  • DNA Mismatch Repair
  • Female
  • Genetic Predisposition to Disease*
  • Germ-Line Mutation
  • Humans
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / prevention & control
  • Risk Assessment

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human