title: Germline BRCA1-2 mutations in non-Ashkenazi families with double primary breast and ovarian cancer.
abstract: OBJECTIVE
  Ashkenazi women with double primary breast and ovarian cancer have a high prevalence (57%) of germline Jewish founder mutations in the BRCA1 (185delAG, 5382insC) and BRCA2 (6174delT) genes. The purpose of this study was to determine the frequency and type of BRCA1-2 mutations in non-Ashkenazi families with at least one member having double primary breast and ovarian cancer.
  
  
  METHODS
  Women at increased risk for cancer based upon their family history were enrolled at the University of Texas Southwestern Familial Cancer Registry between 1992 and 2000. Blood samples from patients desiring genetic testing were sent for complete DNA sequencing of the BRCA1 and BRCA2 genes. Families with a member having both breast and ovarian cancer were identified and clinical data were obtained.
  
  
  RESULTS
  Sixty-two (7%) of 900 enrolled families were non-Ashkenazi and had at least one member with double primary breast and ovarian cancer. Twenty-one families had members who underwent genetic testing; 41 did not. Thirteen (62%) families had a germline BRCA1 (n = 11) or BRCA2 (n = 2) mutation; only one Jewish founder mutation (185delAG) was detected. Eight (38%) families tested negative. Six (86%) of seven women undergoing genetic testing who themselves had double primary breast and ovarian cancer were BRCA1-2 mutation carriers.
  
  
  CONCLUSIONS
  Germline BRCA1-2 mutations are common in non-Ashkenazi families with a member having double primary breast and ovarian cancer. These mutations occurred throughout both genes, emphasizing the need for comprehensive sequencing. One family had the BRCA2 6985delCT mutation, which lies beyond the "ovarian cancer cluster" region.
authors.affiliation: Harold C. Simmons Comprehensive Cancer Center and Familial Cancer Registry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8593, USA. John.Schorge@UTSouthwestern.edu
authors.forename: J O
authors.initials: JO
authors.lastname: Schorge
authors.forename: N M
authors.initials: NM
authors.lastname: Mahoney
authors.forename: D S
authors.initials: DS
authors.lastname: Miller
authors.forename: R L
authors.initials: RL
authors.lastname: Coleman
authors.forename: C Y
authors.initials: CY
authors.lastname: Muller
authors.forename: D M
authors.initials: DM
authors.lastname: Euhus
authors.forename: G E
authors.initials: GE
authors.lastname: Tomlinson
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*