Literature Review ofBARD1as a Cancer Predisposing Gene with a Focus on Breast and Ovarian Cancers

Soon after the discovery ofBRCA1andBRCA2over 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 pathogenicBARD1variants likely conferred a low-moderate risk to hereditary breast cancer, but this association is inconsistent. Here, we review studies ofBARD1as 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 ofBARD1to identify potentially pathogenic germline variants in adult hereditary cancer syndromes; (ii) biological assays ofBARD1variants to assess their effect on protein function; and (iii) association studies ofBARD1variants in family-based and case-control study groups to assess cancer risk. In conclusion,BARD1is likely to be a low-moderate penetrance breast cancer risk gene.