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[Cancer Research 60, 4513-4518, August 15, 2000]
© 2000 American Association for Cancer Research

Molecular Biology and Genetics

The Frequency of Germ-line Mutations in the Breast Cancer Predisposition Genes BRCA1 AND BRCA2 in Familial Prostate Cancer1

Simon A. Gayther, Karen A. F. de Foy, Patricia Harrington, Paul Pharoah, William D. Dunsmuir, Stephen M. Edwards, Cheryl Gillett, Audrey Ardern-Jones, David P. Dearnaley, Douglas F. Easton, Deborah Ford, Robert J. Shearer, Roger S. Kirby, Anna L. Dowe, Joanne Kelly, Michael R. Stratton, Bruce A. J. Ponder, Diana Barnes, Rosalind A. Eeles3 and The Cancer Research Campaign/British Prostate Group United Kingdom Familial Prostate Cancer Study Collaborators,2

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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