Genetic Predisposition to Breast and Ovarian Cancers: How Many and Which Genes to Test?

Int J Mol Sci. 2020 Feb 8;21(3):1128. doi: 10.3390/ijms21031128.


Breast and ovarian cancers are some of the most common tumors in females, and the genetic predisposition is emerging as one of the key risk factors in the development of these two malignancies. BRCA1 and BRCA2 are the best-known genes associated with hereditary breast and ovarian cancer. However, recent advances in molecular techniques, Next-Generation Sequencing in particular, have led to the identification of many new genes involved in the predisposition to breast and/or ovarian cancer, with different penetrance estimates. TP53, PTEN, STK11, and CDH1 have been identified as high penetrance genes for the risk of breast/ovarian cancers. Besides them, PALB2, BRIP1, ATM, CHEK2, BARD1, NBN, NF1, RAD51C, RAD51D and mismatch repair genes have been recognized as moderate and low penetrance genes, along with other genes encoding proteins involved in the same pathways, possibly associated with breast/ovarian cancer risk. In this review, we summarize the past and more recent findings in the field of cancer predisposition genes, with insights into the role of the encoded proteins and the associated genetic disorders. Furthermore, we discuss the possible clinical utility of genetic testing in terms of prevention protocols and therapeutic approaches.

Keywords: cancer predisposition; cancer risk; gene panels; hereditary breast and ovarian cancer; next-generation sequencing.

Publication types

  • Review

MeSH terms

  • Breast Neoplasms / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Ovarian Neoplasms / genetics*
  • PTEN Phosphohydrolase / genetics
  • Tumor Suppressor Protein p53 / genetics


  • Tumor Suppressor Protein p53
  • PTEN Phosphohydrolase