title: Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer.
abstract: The lifetime risk of breast cancer may approach 80-90% in women who have germline mutations of either of two genes, BRCA1 or BRCA2. A single BRCA1 mutation, 185delAG, has been noted in approximately 20% of Ashkenazi Jewish women with early onset breast cancer and in 0.9% of the Ashkenazi population. We recently detected a 6174delT frameshift mutation in BRCA2 in an hereditary breast cancer kindred of Ashkenazi Jewish ancestry. Here, we investigated the frequency of this mutation in 200 women with early-onset breast cancer. Six of 80 Ashkenazi Jewish women (8%) diagnosed with breast cancer before the age of 42, wer heterozygous for the 6174delT mutation, compared to none of 93 non-Jewish women diagnosed with breast cancer at the same age (P = .005). These cases were ascertained without regard to family history. Two of 27 (7%) additional Jewish families in which the proband was diagnosed with breast cancer at age 42 to 50 and had a family history of breast or ovarian cancer had germline 6174delT mutations. The results of this report suggest that a recurrent mutation of BRCA1 and a recurrent mutation BRCA2 together may account for over a quarter of all early-onset breast cancer in the setting of a personal or family history of ovarian cancer in Ashkenazi Jewish women.
authors.affiliation: Department of Human Genetics, Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: S
authors.initials: S
authors.lastname: Neuhausen
authors.forename: T
authors.initials: T
authors.lastname: Gilewski
authors.forename: L
authors.initials: L
authors.lastname: Norton
authors.forename: T
authors.initials: T
authors.lastname: Tran
authors.forename: P
authors.initials: P
authors.lastname: McGuire
authors.forename: J
authors.initials: J
authors.lastname: Swensen
authors.forename: H
authors.initials: H
authors.lastname: Hampel
authors.forename: P
authors.initials: P
authors.lastname: Borgen
authors.forename: K
authors.initials: K
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Skolnick
authors.forename: D
authors.initials: D
authors.lastname: Shattuck-Eidens
authors.forename: S
authors.initials: S
authors.lastname: Jhanwar
authors.forename: D
authors.initials: D
authors.lastname: Goldgar
authors.forename: K
authors.initials: K
authors.lastname: Offit
mesh_terms: D000328:Adult; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D001483:Base Sequence; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D017931:DNA Primers; D005190:Family; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007585:Jews / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D017931:DNA Primers; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors