DNA double strand break repair and its association with inherited predispositions to breast cancer.
Mutations in BRCA1 account for the majority of familial aggregations of early onset breast and ovarian cancer (~70%) and about 1/5 of all early onset breast cancer families; in contrast, mutations in BRCA2 account for a smaller proportion of breast/ovarian cancer families and a similar proportion of early onset breast cancer families. BRCA2 has also been shown to be associated with a much more pleiotropic disease spectrum compared to BRCA1. Since the identification of both BRCA1 and BRCA2 investigations into the functions of these genes have revealed that both are associated with the maintenance of genomic integrity via their apparent roles in cellular response to DNA damage, especially their involvement in the process of double strand DNA break repair. This review will focus on the specific roles of both genes and how functional differences may account for the diverse clinical findings observed between families that harbour BRCA1 or BRCA2 mutations.
Scott
Rodney J
RJ
Discipline of Medical Genetics, School of Biomedical Sciences, Faculty of Health, University of Newcastle and the Hunter Medical Research Institute, Newcastle, Australia and Division of Genetics, Hunter Area Pathology Service, John Hunter Hospital, Newcastle, Australia. Rodney.Scott@hunter.health.nsw.gov.au.