title: 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.
  
  
  METHODS
  Genetic testing of a subset of cases from an ongoing study of ovarian cancer and of controls.
  
  
  METHODS
  A community-based case-control incidence study.
  
  
  METHODS
  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.
  
  
  METHODS
  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
authors.affiliation: Department of Clinical Epidemiology, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Modan
authors.forename: E
authors.initials: E
authors.lastname: Gak
authors.forename: R B
authors.initials: RB
authors.lastname: Sade-Bruchim
authors.forename: G
authors.initials: G
authors.lastname: Hirsh-Yechezkel
authors.forename: L
authors.initials: L
authors.lastname: Theodor
authors.forename: F
authors.initials: F
authors.lastname: Lubin
authors.forename: G
authors.initials: G
authors.lastname: Ben-Baruch
authors.forename: U
authors.initials: U
authors.lastname: Beller
authors.forename: A
authors.initials: A
authors.lastname: Fishman
authors.forename: R
authors.initials: R
authors.lastname: Dgani
authors.forename: J
authors.initials: J
authors.lastname: Menczer
authors.forename: M
authors.initials: M
authors.lastname: Papa
authors.forename: E
authors.initials: E
authors.lastname: Friedman
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D016022:Case-Control Studies; D004586:Electrophoresis; D005091:Exons; D005260:Female; D006579:Heterozygote; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics*; D009154:Mutation; D010051:Ovarian Neoplasms / Q000208:ethnology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D019313:BRCA1 Protein