HIGH-FREQUENCY OF BRCA1 185DELAG MUTATION IN OVARIAN-CANCER IN ISRAEL

Objective.-To determine the role of BRCA1 185delAG mutation in ovarian carcinogenesis. Design.-Genetic testing of a subset of cases from an ongoing study of ovarian cancer and of controls. Setting.-A community- based case-control incidence study. Subjects.-Seventy-nine patients wi th ovarian cancer, 62 hospitalized women without cancer (controls), an d 120 healthy women participating in a fragile X screening program (al so controls), examined for the presence of germline BRCA1 185delAG mut ation. Main Outcome Measures.-Polymerase chain reaction-amplified BRCA 1 exon 2 fragments generated from patients' and controls' blood sample s, analyzed by heteroduplex gel shift assay and direct sequence analys es. Results.-The 185delAG mutation was detected in 38.9% (7/18) of ova rian cancer patients with familial history, and 13.1% (8/61) of family history-negative ovarian cancer cases. Only 1 carrier was detected am ong the 120 healthy controls, and none in the hospital controls. A sig nificant difference in mutation carrier rates between family history-n egative cases and control groups of 120 and 62 subjects was identified (Fisher exact test, P=.001 and P=.003, respectively). The median age (+/-SE) at disease diagnosis was tower among both familial and family history-negative mutation carriers, as compared with mutation-negative , family history-negative cases-50 (+/-1.4) vs 60.5 (+/-3.5) years old , respectively (hazard ratio, 1.68; 95% confidence interval, 0.94-3.01 ). Conclusions.-Our data are preliminary but suggest that BRCA1 185del AG germline mutation is frequent in Israeli ovarian cancer patients, i rrespective of family history, and may confer an early-onset phenotype of ovarian cancer.