Department of Pharmacy, China Medical University, Taichung, Taiwan.
Clin Chim Acta. 2010 Sep 6;411(17-18):1232-7. doi: 10.1016/j.cca.2010.04.028. Epub 2010 May 9.
Recent genome-wide association studies have identified several independent single nucleotide polymorphisms (SNPs) strongly associated with prostate cancer (PCa) risk. However, their individual and cumulative associations with clinicopathologic characteristics of the disease remain inconclusive.
We systematically evaluated 20 PCa risk SNPs in a cohort of 320 localized PCa patients receiving radical prostatectomy, and the associations of these variants with age at diagnosis, preoperative prostate-specific antigen concentration, Gleason score, pathologic stage, surgical margin, and lymph node metastasis were evaluated.
Eight SNPs, rs10486567 at 7p15, rs6465657 at 7q21, rs6983267, rs1447295, and rs4242382 at 8q24, 10993994 at 10q11, rs4430796 at 17q12, and rs266849 at 19q13, were significantly (P< or =0.048) associated with some specific clinicopathologic features. In combination of these 8 SNPs, men who carried 4 or 5, or more than 5 unfavorable alleles had an increasing likelihood of adverse clinicopathologic features, as compared with men who carried fewer than 4 unfavorable alleles (P for trend, 0.031, <0.001, 0.006, and 0.003, for Gleason scores 8-10, advanced pathologic stage, positive surgical margin, and lymph node metastasis, respectively).
Our results suggested that loci associated with PCa risk might also have a cumulative and significant association with disease aggressiveness.
最近的全基因组关联研究已经确定了几个与前列腺癌（PCa）风险强烈相关的独立单核苷酸多态性（SNP）。然而，它们与疾病的临床病理特征的个体和累积关联仍然没有定论。
我们系统地评估了 320 例接受根治性前列腺切除术的局限性 PCa 患者队列中的 20 个 PCa 风险 SNP，评估了这些变体与诊断时年龄、术前前列腺特异性抗原浓度、Gleason 评分、病理分期、手术切缘和淋巴结转移的关联。
rs10486567 位于 7p15、rs6465657 位于 7q21、rs6983267、rs1447295 和 rs4242382 位于 8q24、10993994 位于 10q11、rs4430796 位于 17q12 和 rs266849 位于 19q13 的 8 个 SNP 与一些特定的临床病理特征显著相关（P<或=0.048）。在这 8 个 SNP 的组合中，携带 4 个或 5 个或更多不利等位基因的男性比携带少于 4 个不利等位基因的男性更有可能出现不良的临床病理特征（趋势 P 值，0.031、<0.001、0.006 和 0.003，分别用于 Gleason 评分 8-10、晚期病理分期、阳性手术切缘和淋巴结转移）。
我们的结果表明，与 PCa 风险相关的基因座也可能与疾病侵袭性有累积和显著的关联。
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