Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer.
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.
Neuhausen
S
S
Department of Human Genetics, Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Gilewski
T
T
Norton
L
L
Tran
T
T
McGuire
P
P
Swensen
J
J
Hampel
H
H
Borgen
P
P
Brown
K
K
Skolnick
M
M
Shattuck-Eidens
D
D
Jhanwar
S
S
Goldgar
D
D
Offit
K
K
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*
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D017931:DNA Primers; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors