BRCA1 and BRCA2: 1994 and beyond

Abstract

In the ten years since the discovery of BRCA1 and BRCA2, genetic testing for breast and ovarian cancer susceptibility has become integrated into the practice of clinical oncology. Attempts to identify a third breast cancer susceptibility locus (BRCA3) have so far been unsuccessful. This is probably because no single gene can account for the remainder of families that show a high incidence of breast cancer that is not associated with BRCA1 or BRCA2. In general, the genes that have been identified as being associated with hereditary breast cancer (BRCA1, BRCA2, TP53, CHK2 and ATM) are involved in the maintenance of genomic integrity and DNA repair. The risk of developing cancer is not identical for all carriers of BRCA1 and BRCA2 mutations. Risk can be influenced by allelic heterogeneity, modifier genes, and environmental and hormonal cofactors.