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

Abstract

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 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.

Main outcome measures: 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.

Results: 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).

Conclusions: 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