The contribution of BRCA1 and BRCA2 to ovarian cancer

Germline mutations of the BRCA1 and BRCA2 genes confer a high life-time risk of ovarian cancer. They represent the most significant and well characterised genetic risk factors so far identified for the disease. The frequency with which BRCA1/2 mutations occur in families containing multiple cases of ovarian cancer or breast and ovarian cancer, and in population-based ovarian cancer series varies geographically and between different ethnic groups. There are differences in the frequency of common mutations and in the presence of specific founder mutations in different populations. BRCA1 and BRCA2 are responsible for half of all families containing two or more ovarian cancer cases. In population-based studies, BRCA1 and BRCA2 mutations are present in 5-15% of all ovarian cancer cases. Often, individuals in which mutations are identified in unselected cases have no family history of either ovarian or breast cancer. The ability to identify BRCA1/2 mutations has been one of the few major success stories over the last few years in the clinical management of ovarian cancer. Currently, unaffected individuals can be screened for mutations if they have a family history of the disease. If a mutation is identified in the family, and if an individual is found be a mutation carrier, they can be offered clinical intervention strategies that can dramatically reduce their ovarian cancer risks. In some populations with frequent founder mutations screening may not be dependent on whether a mutation is identified in an affected relative.