Abstract:
: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 < or = 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 (< or = 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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Gayther SA,de Foy KA,Harrington P,Pharoah P,Dunsmuir WD,Edwards SM,Gillett C,Ardern-Jones A,Dearnaley DP,Easton DF,Ford D,Shearer RJ,Kirby RS,Dowe AL,Kelly J,Stratton MR,Ponder BA,Barnes D,Eeles RAsubject
Has Abstractpub_date
2000-08-15 00:00:00pages
4513-8issue
16eissn
0008-5472issn
1538-7445journal_volume
60pub_type
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