Unique genetic characteristics of BRCA mutation carriers in a cohort of Arab American women

1541 Background: Worldwide ethnic variations in the distribution of BRCA1 and BRCA2 mutations of breast cancer patients have been recently recognized. This has led to investigations of the epidemiology, genetics and clinical characteristics of BRCA positive individuals within specific populations. This study aims to describe the findings of BRCA genetic testing in a cohort of Arab American women. Methods: A total of 73 women of Arab ancestry were evaluated in the Beaumont Cancer Genetics Program from Jan 2008 to Jan 2013. Criteria for genetic testing included a personal or family history suggestive of Hereditary Breast and Ovarian Cancer Syndrome (HBOC). Patients underwent comprehensive genetic counseling, followed by full sequence analysis for germline mutations in BRCA1 and BRCA2. Results: 63 women of Arab ancestry underwent genetic testing for BRCA1 and BRCA2. 13 (21%) patients were found to be mutation carriers, of whom 10 (16%) of the 63 had deleterious mutations (7 in BRCA2, and 3 in BRCA1), and 3 (5%) had variants of undetermined significance (VUS) in BRCA2. Of the 10 patients with deleterious mutations, 4 (40%) unrelated individuals had the same mutation, 5804del4, in exon 11 of BRCA2. The remaining patients had deleterious mutations in exon 2, exon 20, and exon 13 of BRCA2; one patient had a BRCA1 and BRCA2 mutation (exon 18). 7 of 10 patients with deleterious mutations had a cancer diagnosis, of which 5 had breast cancer, 1 had ovarian cancer, 1 had pancreatic cancer, and 3 were unaffected. Conclusions: This study demonstrates that BRCA mutations (predominantly in BRCA2) were seen in a significant proportion of Arab American women undergoing genetic testing for HBOC. A mutation in BRCA2, 5804del4, was seen in nearly half (4/10) of the carriers of deleterious mutations. This mutation, in exon 11, has not previously been associated with Arab ethnicity and may represent a founder mutation. Knowledge of the genetic spectrum, frequency, and clinical characteristics of BRCA mutation carriers will lead to greater understanding of hereditary cancer in Arab American women.