Common mutations in BRCA1 and BRCA2 do not contribute to early prostate cancer in Jewish men.
BACKGROUND
Families with a high incidence of hereditary breast cancer, and subsequently shown to have terminating mutations in BRCA1 or BRCA2, appear to have a higher incidence of prostate cancer among male relatives. We aimed to determine whether the common germline mutations of BRCA1 or BRCA2 in Ashkenazi Jewish men predisposed them to prostate cancer.


METHODS
We examined genomic DNA from 83 (for BRCA1 185delAG) or 82 (for BRCA2 6174delT) Ashkenazi Jewish prostate cancer patients, most of whom were treated at a relatively young age, for the most common germline mutation in each gene seen in the Ashkenazi population.


RESULTS
Our study should have been able to detect a 4-5-fold increase in the risk of prostate cancer due to mutation of BRCA1 or BRCA2. However, only one (1.15%; 95% confidence interval, 0-3.6%) of the patients was heterozygous for the BRCA1 mutant allele, and only two were heterozygous for the BRCA2 mutation (2.4%; 95% confidence interval, 0-6.2%).


CONCLUSIONS
The incidence of each of the germline mutations in these prostate cancer patients closely matched their incidence (about 1%) in the general Ashkenazi Jewish population. This suggests that unlike cases of breast and ovarian cancers, mutations in BRCA1 or BRCA2 do not significantly predispose men to prostate cancer.
Department of Pathology and Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York, USA.
K L
KL
Nastiuk
M
M
Mansukhani
M B
MB
Terry
P
P
Kularatne
M A
MA
Rubin
J
J
Melamed
M D
MD
Gammon
M
M
Ittmann
J J
JJ
Krolewski
D000328:Adult; D024682:BRCA2 Protein; D005060:Europe / Q000208:ethnology; D005091:Exons; D019398:Genes, BRCA1; D005819:Genetic Markers; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D007438:Introns; D007585:Jews; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009519:New York City; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
D024682:BRCA2 Protein; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors