FAMILIAL BREAST-CANCER - APPROACHING THE ISOLATION OF A SUSCEPTIBILITY GENE

Family history is recognized widely as a significant risk factor for t he development of breast cancer. A gene (BRCA1), mutations in which co nfer susceptibility to early-onset breast and ovarian cancer, has been mapped to chromosome 17q12-21. An intensive search for this gene is c urrently underway in a number of laboratories. Recent data support the hypothesis that BRCA1 is a tumor suppressor gene that may be importan t in the development of both inherited and sporadic breast and ovarian cancers. Genetic and physical maps of the BRCA1 candidate region larg ely have been completed and efforts are being directed at identificati on of candidate genes from within this region. A small number of famil ies recently have received results of genetic-linkage testing, indicat ing which family members likely are to be carriers of a germline BRCA1 mutation, and, therefore, have a lifetime risk of developing breast c ancer of approximately 85%. The imminent isolation of BRCA1 will make predictive testing for breast cancer a reality for many women and like ly will pave the way for novel diagnostic and therapeutic strategies i n the future.