Prevalence of the BRCA2 6174 del T mutation in Israeli uveal melanoma patients

Substantial differences exist in the incidence rates of uveal melanoma (UM) among Israeli Jewish subpopulations: high in immigrants from North America and Europe (Ashkenazic) and low in immigrants from Africa and Asia (Sepharadic). This trend persists in Israeli-born individuals when stratified by their ancestral place of birth. There have been several anecdotal reports of uveal melanoma occurring in breast cancer families with mutations in the BRCA2 gene as well as one systematic study reporting BRCA2 mutations in UM. A single BRCA2 mutation, 6174 del T, occurs in about 1% of the Ashkenazic population and rarely in non-Ashkenazic. To assess the contribution of this germline mutation to uveal melanoma in Jewish Israeli patients, we tested this relationship through analysis of blood samples from a series of UM patients. A total of 153 cases (84 female, 69 male) were available for study, which represents 30% of all cases of UM diagnosed in Israel during the period 1984-1999 (82% for the period 1992-1999). Of the 143 UM patients for which a result could be obtained (4 due to refusals, 6 due to damage to the blood sample), 4 (2.8%, 95% confidence interval [CI] 0-5.6) carried the 6174 del T mutation. Assuming a population frequency of the mutation of 1% as estimated among Ashkenazic Jews in the United States, the probability of observing 4 or more carriers with the 6174 del T mutation, assuming no relationship between uveal melanoma and BRCA2, is 0.057. Although our study confirms the relationship between uveal melanoma and BRCA2, it is clear that the 6174 del T mutation accounts for only a small fraction of all Israeli UM cases. Therefore, BRCA2 mutations are likely to account for an even smaller proportion in populations with low frequencies of BRCA2 alterations.