ICARE Newsletter Summer 2015

Location and Type of BRCA1/2 Mutation May Impact Breast and Ovarian Cancer Risks


A study of almost 20,000 BRCA1 carriers and 12,000 BRCA2 carriers demonstrated differences in breast and ovarian cancer risks depending on the location and type of mutation. Although all regions are associated with increased risk for breast and ovarian cancers among BRCA1/2 carriers, there were specific regions that were associated with even higher cancer risks. Specifically, within BRCA1, there were three breast cancer cluster regions located at: 1) c.179-c.505; 2) c.4328-c.4945; and 3) c.5261-c.5563. There was also an ovarian cancer cluster region from c.1380-c.4062.  In BRCA2, there were multiple breast cancer cluster regions spanning c.1-c.596, c.772-c.1806 and c.7394-c.8904.  There were also ovarian cancer cluster regions located at: 1) c.3249-c.5681, adjacent to c.5946delT (i.e., 6174delT) and 2) c6645-c.7471. Furthermore, nonsense mutations (point mutations resulting in a shorter and unfinished protein product) were associated with earlier age of breast cancer diagnosis and differential breast or ovarian cancer risks for both BRCA1 and BRCA2. Overall, this worldwide effort represents the largest study to date to evaluate breast and ovarian cancer risks by location and type of BRCA1/2 mutation. Although results suggest variations in risk, these data require validation prior to BRCA1/2 carriers using the information for cancer prevention decision-making.

Rebbeck TR et al. Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer. JAMA. 2015 Apr 7;313(13):1347-61. PMID: 25849179.

Permanent link to this article: https://inheritedcancer.net/4nls2015/