Literature Review of BARD1 as a Cancer Predisposing Gene with a Focus on Breast and Ovarian Cancers

Genes (Basel). 2020 Jul 27;11(8):856. doi: 10.3390/genes11080856.


Soon after the discovery of BRCA1 and BRCA2 over 20 years ago, it became apparent that not all hereditary breast and/or ovarian cancer syndrome families were explained by germline variants in these cancer predisposing genes, suggesting that other such genes have yet to be discovered. BRCA1-associated ring domain (BARD1), a direct interacting partner of BRCA1, was one of the earliest candidates investigated. Sequencing analyses revealed that potentially pathogenic BARD1 variants likely conferred a low-moderate risk to hereditary breast cancer, but this association is inconsistent. Here, we review studies of BARD1 as a cancer predisposing gene and illustrate the challenge of discovering additional cancer risk genes for hereditary breast and/or ovarian cancer. We selected peer reviewed research articles that focused on three themes: (i) sequence analyses of BARD1 to identify potentially pathogenic germline variants in adult hereditary cancer syndromes; (ii) biological assays of BARD1 variants to assess their effect on protein function; and (iii) association studies of BARD1 variants in family-based and case-control study groups to assess cancer risk. In conclusion, BARD1 is likely to be a low-moderate penetrance breast cancer risk gene.

Keywords: BARD1; breast cancer; cancer predisposing gene; hereditary cancer syndromes; multi-gene panel testing; next-generation sequencing; ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Female
  • Genetic Predisposition to Disease*
  • Germ-Line Mutation*
  • Humans
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology*
  • Tumor Suppressor Proteins / genetics*
  • Ubiquitin-Protein Ligases / genetics*


  • Tumor Suppressor Proteins
  • BARD1 protein, human
  • Ubiquitin-Protein Ligases