The frequency of founder mutations in the BRCA1, BRCA2, and APC genes in Australian Ashkenazi Jews - Implications for the generality of US populationdata

BACKGROUND. Several studies have shown that Ashkenazi Jews in the United St ates and Israel have a high prevalence of the founder mutations BRCA1 185de lAG, BRCA1 5382insC, BRCA2 6174deIT, and APC I1307K at frequencies of 1.0-1 .1%, 0.2-0.3%, 0.6-1.4%, and 6.1-7.0%, respectively. The objective of this study was to compare the prevalence of these alleles in the Australian Jewi sh population with that of U.S. Jews. Australian Jews have a different hist ory of migration, with less opportunity for changes in allele frequency due to conversion or intermarriage with non-Jewish Australians. The results ob tained therefore can be used to assess whether U.S. data can be generalized to other Jewish populations. SUBJECTS AND METHODS. Subject samples were ascertained through a screening program for Tay-Sachs disease as part of a community-based screening progra m in New South Wales and Victoria. DNA extracted from 1200 deidentified blo od samples was tested using amplification refractory mutation system polyme rase chain reaction. RESULTS. The allele frequencies found were as follows: BRCA1 185delAG 1.25W (95% confidence interval [CII, 0.62-1.88%), BRCA1 5382insC 0.25% (95% CI, 0-0.53%), BRCA2 6174delT 1.08% (95% CI, 0.50-1.67%), and APC I1307K 8.67% ( 95% CI, 7.07-10.26%). The prevalence of breast carcinoma predisposition all eles therefore is greater than 2.5% in Australian Ashkenazim. CONCLUSIONS. There were no significant differences between the allele frequ encies in Australian Ashkenazim and those identified in other studies with similar ascertainment strategies, despite the different migration patterns of Australian Jews. This suggests the broad applicability of the U.S. and I sraeli data, not only to Australian Ashkenazim, but also to Ashkenazi commu nities throughout the world. (C) 2001 American Cancer Society.