High frequency of BRCA1 185delAG mutation in ovarian cancer in Israel. National Israel Study of Ovarian Cancer.

Abstract

To determine the role of BRCA1 185delAG mutation in ovarian carcinogenesis. Genetic testing of a subset of cases from an ongoing study of ovarian cancer and of controls. A community-based case-control incidence study. Seventy-nine patients with ovarian cancer, 62 hospitalized women without cancer (controls), and 120 healthy women participating in a fragile X screening program (also controls), examined for the presence of germline BRCA1 185delAG mutation. Polymerase chain reaction-amplified BRCA1 exon 2 fragments generated from patients' and controls' blood samples, analyzed by heteroduplex gel shift assay and direct sequence analyses. The 185delAG mutation was detected in 38.9% (7/18) of ovarian cancer patients with familial history, and 13.1% (8/61) of family history-negative ovarian cancer cases. Only 1 carrier was detected among the 120 healthy controls, and none in the hospital controls. A significant difference in mutation carrier rates between family history-negative 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 lower 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). Our data are preliminary but suggest that BRCA1 185delAG germline mutation is frequent in Israeli ovarian cancer patients, irrespective of family history, and may confer an early-onset phenotype of ovarian cancer