| Autor: |
Alenezi WM; Department of Human Genetics, McGill University, Montreal, QC H3A 0G4, Canada.; Cancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.; Department of Medical Laboratory Technology, Taibah University, Medina 42353, Saudi Arabia., Fierheller CT; Department of Human Genetics, McGill University, Montreal, QC H3A 0G4, Canada.; Cancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada., Recio N; Department of Human Genetics, McGill University, Montreal, QC H3A 0G4, Canada.; Cancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada., Tonin PN; Department of Human Genetics, McGill University, Montreal, QC H3A 0G4, Canada.; Cancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.; Department of Medicine, McGill University, Montreal, QC H3A 0G4, Canada. |
| Abstrakt: |
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. |
