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Molecular Biology and Genetics |
Cancer Research Campaign Human Cancer Genetics Research Group, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 2QQ, United Kingdom [S. A. G., K. A. F. d. F., P. H., P. P., B. A. J. P.]; Institute of Cancer Research, Surrey SM2 5NG, United Kingdom [W. D. D., S. M. E., D. P. D., J. K., M. R. S., R. A. E.]; Department of Urology, St George’s Hospital, London SW17 0QT, United Kingdom [W. D. D., R. S. K.]; Hedley Atkins/Imperial Cancer Research Fund Breast Pathology Laboratory, Guy’s Hospital, London SE1 9RT, United Kingdom [C. G., D. B.]; Royal Marsden National Health Service Trust, Surrey SM2 5PT, United Kingdom [A. A-J., D. P. D., R. J. S., A. L. D., R. A. E.]; Cancer Research Campaign Genetic Epidemiology Unit, Strangeways Research Laboratory, Cambridge CB1 8RN, United Kingdom [D. F. E.]; and Cancer Research Campaign Section of Epidemiology, Institute of Cancer Research, Surrey SM2 5NG, United Kingdom [D. F.]
Predisposition to prostate cancer has a
genetic component, and there are reports of familial clustering of
breast and prostate cancer. Two highly penetrant genes that predispose
individuals to breast cancer (BRCA1 and
BRCA2) are known to confer an increased risk of prostate
cancer of about 3-fold and 7-fold, respectively, in breast
cancer families. Blood DNA from affected individuals in 38 prostate
cancer clusters was analyzed for germ-line mutations in
BRCA1 and BRCA2 to assess the
contribution of each of these genes to familial prostate cancer.
Seventeen DNA samples were each from an affected individual in families
with three or more cases of prostate cancer at any age; 20 samples were
from one of affected sibling pairs where one was 
67 years at
diagnosis. No germ-line mutations were found in BRCA1.
Two germ-line mutations in BRCA2 were found, and both
were seen in individuals whose age at diagnosis was very young (56
years) and who were members of an affected sibling pair. One is
a 4-bp deletion at base 6710 (exon 11) in a man who had prostate cancer
at 54 years, and the other is a 2-bp deletion at base 5531 (exon 11) in
a man who had prostate cancer at 56 years. In both cases, the wild-type
allele was lost in the patient’s prostate tumor at the
BRCA2 locus. However, intriguingly, in neither case did
the affected brother also carry the mutation. Germ-line mutations in
BRCA2 may therefore account for about 5% of prostate
cancer in familial clusters.
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