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Among Asian countries, Pakistan has the highest rates of breast and ovarian cancer. To assess the contribution of theBRCA1andBRCA2germ line mutations to these high rates, we conducted the first study of 176 Pakistani breast and ovarian cancer patients, selected on family history and on age of diagnosis. ComprehensiveBRCAmutation screening was performed using a range of techniques, including denaturing high-pressure liquid chromatography, single strand conformational polymorphism analysis and protein truncation test, followed by DNA sequencing. Thirty deleterious germ-line mutations were identified in the 176 families (17.0%), including 23 inBRCA1and 7 inBRCA2. Four mutations, 185delAG, 185insA, S1503X and R1835X, were recurrent; these accounted for 52% of all identifiedBRCA1mutations. Haplotype analyses suggested founder effects for 3 of these. The prevalence ofBRCA1orBRCA2mutations was 42.8% for families with multiple cases of breast cancer, and was 50.0% for the breast/ovarian cancer families. The prevalence of mutations was 11.9% for single cases of early-onset breast cancer (≤30 years) and was 9.0% for single cases of early-onset ovarian cancer (≤45 years). Our findings show thatBRCAmutations account for a substantial proportion of hereditary breast/ovarian cancer and early-onset breast and ovarian cancer cases in Pakistan.