Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality.
Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality.
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DOI：
10.1158/1055-9965.epi-11-0236
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发表时间：
2011-09
期刊：
影响因子：
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通讯作者：
Stanford JL
中科院分区：
文献类型：
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作者：
Lin DW;FitzGerald LM;Fu R;Kwon EM;Zheng SL;Kolb S;Wiklund F;Stattin P;Isaacs WB;Xu J;Ostrander EA;Feng Z;Grönberg H;Stanford JL
前列腺癌是男性癌症相关死亡的第二大原因，每年造成3万多人死亡。本研究的目的是测试前列腺癌进展的生物学途径中选定的候选基因的变异是否有助于区分致命前列腺癌高风险患者。在这项假设驱动的研究中，我们在基于人群的1309例前列腺癌患者队列中，对156个候选基因中的937个单核苷酸多态性（snp）进行了基因分型。我们发现了22个与前列腺癌特异性死亡率（PCSM）相关的顶级snp （P≤0.01,FDR≤0.70）。随后的一项验证研究在2,875名前列腺癌患者的独立人群队列中完成。5个snp被证实与PCSM显著相关（P≤0.05），分别位于LEPR、CRY1、RNASEL、IL4和ARVCF基因。与携带0-2个高危基因型的患者相比，携带4-5个高危基因型的患者发生PCSM的风险高出50% (95% CI, 1.2-1.9)，并且风险随着携带高危基因型的数量增加而增加（p趋势= 0.001），校正了已知影响预后的临床病理因素。五种遗传标记被证实与致死性前列腺癌有关。这是首次以人群为基础的研究，证明生殖系遗传变异为前列腺癌特异性生存提供了预后信息。应该评估这种五snp小组对不良结局高风险患者进行分层的临床应用。
Prostate cancer is the second leading cause of cancer-related deaths in men, accounting for over 30,000 deaths annually. The purpose of this study was to test whether variation in selected candidate genes in biological pathways of interest for prostate cancer progression could help distinguish patients at higher risk for fatal prostate cancer. In this hypothesis-driven study, we genotyped 937 single nucleotide polymorphisms (SNPs) in 156 candidate genes in a population-based cohort of 1,309 prostate cancer patients. We identified 22 top-ranking SNPs (P ≤0.01, FDR ≤0.70) associated with prostate cancer-specific mortality (PCSM). A subsequent validation study was completed in an independent population-based cohort of 2,875 prostate cancer patients. Five SNPs were validated (P ≤0.05) as being significantly associated with PCSM, one each in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes. Compared to patients with 0–2 of the at-risk genotypes those with 4–5 at-risk genotypes had a 50% (95% CI, 1.2–1.9) higher risk of PCSM and risk increased with the number of at-risk genotypes carried (Ptrend = 0.001), adjusting for clinicopathological factors known to influence prognosis. Five genetic markers were validated to be associated with lethal prostate cancer. This is the first population-based study to demonstrate that germline genetic variants provide prognostic information for prostate cancer-specific survival. The clinical utility of this five-SNP panel to stratify patients at higher risk for adverse outcomes should be evaluated.