Prevalence of BRCA1 and BRCA2 founder mutations in Brazilian hereditary breast and ovarian cancer families

Abstract

22108 Background: Breast cancer (BC) is a significant health care problem in Brazil and only a few studies have been conducted to verify the contribution of founder mutations in BRCA genes to the occurrence of these tumors, especially in high risk families. Two recent studies in the State of Rio de Janeiro described a higher than expected prevalence of the BRCA founder mutations usually seen in individuals of Ashkenazi Jewish origin in non-Jewish breast cancer-affected women. The largest of these studies, conducted by Gomes et al., described a prevalence of 2.3% of the BRCA1 mutation 5382insC these patients were unselected for family history of the disease. Methods: Patients affected with breast cancer or other tumors of the HBOC spectrum, whose familiy histories fulfilled the ASCO criteria for HBOC and/or who had a prior probability of carryng a BRCA mutation ≥30% (using the Myriad prevalence tables and/or the Penn II model) were recruited from high risk genetics clinics in the cities of Rio de Janeiro and São Paulo. All patients denied Ashkenazi Jewish ancestry. Mutation detection was performed by PCR-amplification of the regions of interest in BRCA1 and BRCA2 followed by DNA sequencing. All mutations were confirmed in an independent sample. Results: A total of 145 unrelated patients were tested. None of them carried the 185delAG or 6174delT mutations in BRCA1 and BRCA2, respectively. Five (5) patients carried the BRCA1 mutation 5382insC in the germline, resulting in a prevalence of 3.44% for this mutation in the HBOC families studied. Conclusions: Testing for the three common BRCA founder mutations in non-Ashkenazi Brazilian women is probably not justified, especially not for the 185delAG and 6174delT mutations; the BRCA1 mutation 5382insC however, was relatively frequent. Additional haplotyping studies will be necessary to determine if these mutants share a common haplotype with those identified in individuals of Ashkenazi origin. No significant financial relationships to disclose.