Gayther S A, de Foy K A, Harrington P, Pharoah P, Dunsmuir W D, Edwards S M, Gillett C, Ardern-Jones A, Dearnaley D P, Easton D F, Ford D, Shearer R J, Kirby R S, Dowe A L, Kelly J, Stratton M R, Ponder B A, Barnes D, Eeles R A
Cancer Research Campaign Human Cancer Genetics Research Group, University of Cambridge, Addenbrook's Hospital, United Kingdom.
Cancer Res. 2000 Aug 15;60(16):4513-8.
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.
前列腺癌的易感性具有遗传成分，并且有关于乳腺癌和前列腺癌家族聚集性的报道。已知两个使个体易患乳腺癌的高 penetrance 基因（BRCA1 和 BRCA2），在乳腺癌家族中分别使患前列腺癌的风险增加约 3 倍和 7 倍。对 38 个前列腺癌聚集家族中受影响个体的血液 DNA 进行分析，以检测 BRCA1 和 BRCA2 的种系突变，从而评估这些基因对家族性前列腺癌的贡献。17 个 DNA 样本分别来自任何年龄有三例或更多前列腺癌病例的家族中的受影响个体；20 个样本来自一对受影响的同胞兄弟中的一个，其中一人在诊断时年龄≤67 岁。在 BRCA1 中未发现种系突变。在 BRCA2 中发现了两个种系突变，且均见于诊断时年龄非常小（≤56 岁）且为受影响同胞兄弟之一的个体。一个是一名 54 岁患前列腺癌男性在第 6710 位碱基（外显子 11）处的 4 碱基缺失，另一个是一名 56 岁患前列腺癌男性在第 5531 位碱基（外显子 11）处的 2 碱基缺失。在这两种情况下，患者前列腺肿瘤中 BRCA2 基因座的野生型等位基因均缺失。然而，有趣的是，在这两种情况下，受影响的兄弟均未携带该突变。因此，BRCA2 的种系突变可能占家族性聚集性前列腺癌的约 5%。
