Cancers associated with BRCA1 and BRCA2 mutations other than Breast and Ovarian

SUMMARY:Approximately 5-10% of all Breast and Ovarian cancers are caused by inherited genetic factors and are typically the result from inherited mutations in either the BRCA1 or BRCA2 gene. BRCA1 and BRCA2 are tumor suppressor genes located on chromosome 17 and chromosome 13 respectively. They control cell growth by repairing DNA damage and thus prevent tumor development. Mutations in these genes predispose an individual to develop malignant tumors. The presence of BRCA1 and BRCA2 mutations can significantly increase the lifetime risk for developing Breast and Ovarian cancer, as high as 85% and 40% respectively. While the association of BRCA1 and BRCA2 mutations with Breast and Ovarian cancer risks is well-established, the potential association of these mutations with other cancers has remained unclear. This study was conducted to evaluate the incidence of cancers other than Breast and Ovarian cancer, in known BRCA1 and BRCA2 mutation carriers. The study population included 1072 patients who had received genetic counseling at the UT MD Anderson Cancer Center between 1997 and 2013 and had a confirmed BRCA1 (N=613) or BRCA2 (N=459) mutation. The authors then compared the cancer incidence of the study population with the United States Cancer Statistics. The expected and observed numbers of cancer cases were calculated at 5 year intervals to take into consideration different age-related incidence rates. Standardized Incidence Ratios (SIRs) for each cancer type was then calculated for the entire sample and for BRCA1 mutation carriers and BRCA2 mutation carriers separately. {Standardized Incidence Ratio (SIR) is used to determine if the occurrence of cancer in a relatively small population is high or low. A SIR of 1 would indicate no increase or decrease, SIR of 1.5 indicates an excess of 50%, SIR of 2 indicates an excess of 100%}. Among the study population, 1177 cancers comprising 30 different cancer types were identified. There was no significant increase in cancers other than Breast and Ovarian cancer in individuals with BRCA1 mutation, but there was a trend of increasing incidence of Melanoma in BRCA1 mutation carriers, compared to general population. Individuals with BRCA2 mutation however had significantly higher incidence of Pancreatic cancer in both men and women (SIR= 21.7; P < 0.001), Prostate cancer in men (SIR= 4.9; P = 0.002) and a trend of increasing incidence of Cervical cancer, compared to general population. The authors concluded that their findings support the NCCN practice guidelines for this patient population which includes screening for male Breast cancer, Prostate cancer and Melanoma, acknowledging that specific screening guidelines for Pancreatic cancer do not exist. Mersch J, Jackson MA, Park M, et al. Cancer 2015; 121:269-275