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
OBJECTIVE: To determine the role of BRCA1185delAG 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 BRCA1185delAG 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 cancerpatients 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 BRCA1185delAG germline mutation is frequent in Israeli ovarian cancerpatients, irrespective of family history, and may confer an early-onset phenotype of ovarian cancer
Authors: R Moslehi; W Chu; B Karlan; D Fishman; H Risch; A Fields; D Smotkin; Y Ben-David; J Rosenblatt; D Russo; P Schwartz; N Tung; E Warner; B Rosen; J Friedman; J S Brunet; S A Narod Journal: Am J Hum Genet Date: 2000-03-16 Impact factor: 11.025
Authors: E Levy-Lahad; R Catane; S Eisenberg; B Kaufman; G Hornreich; E Lishinsky; M Shohat; B L Weber; U Beller; A Lahad; D Halle Journal: Am J Hum Genet Date: 1997-05 Impact factor: 11.025
Authors: R Gershoni-Baruch; Y Patael; A Figer; L Kasinetz; E Kadouri; R Bruchim Bar Sade; E Friedman Journal: Br J Cancer Date: 2000-07 Impact factor: 7.640