GWAS-identified colorectal cancer susceptibility locus associates with disease prognosis
GWAS-identified colorectal cancer susceptibility locus associates with disease prognosis
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GWAS 确定的结直肠癌易感位点与疾病预后相关。
DOI：
10.1016/j.ejca.2011.02.004
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发表时间：
2011-07-01
影响因子：
8.4
通讯作者：
Chen, Zhinan
中科院分区：
文献类型：
--
作者：
Xing, Jinliang;Myers, Ronald E.;Chen, Zhinan
目的：大量的证据表明，癌症发展的危险因素也可能调节癌症的临床结果。最近的全基因组关联（GWA）研究确定了几个单核苷酸多态性（SNP）易患结直肠癌（CRC）。鉴于这些变异在结直肠癌中的关键重要性，我们试图评估它们与疾病临床结局的关系。实验设计：在一个包括380名中国结直肠癌患者的特征性队列中，我们对在以前的多阶段GWA研究中鉴定的7个SNP进行基因分型，并分析它们与患者复发和生存的关系。染色体15 q13上的一个SNP rs 4779584与死亡风险降低相关，风险比（HR）为0.33（95%置信区间[CI] 0.15-0.72，P = 0.007）。另一个位于染色体10 p14基因荒漠区的SNP rs 10795668与复发风险降低相关，HR为0.55（95%CI 0.30-1.00，P = 0.05）。在分层分析中，这种关联仅在接受化疗的患者中明显（HR = 0.32，95% CI 0.14-0.78，P = 0.01，对数秩P = 0.004），但在未接受化疗的患者中不明显（HR = 1.08，95% CI 0.43-2.73，P = 0.87，对数秩P = 0.66）。此外，我们发现化疗对CRC复发的影响仅在含有变异基因型的患者中明显（HR = 0.35，95%CI 0.13-0.94，P = 0.04），但在rs 10795668野生型基因型患者中不明显。进一步的分析表明，rs 10795668和化疗之间的临界显着的交互作用（P交互= 0.05）patient recurrence.Conclusions：我们的数据表明，rs 10795668，结直肠癌的易感性变异GWA研究确定，可能会被用来作为一个生物标志物，以确定化疗后复发的高风险的结直肠癌患者。(C)2011爱思唯尔有限公司版权所有。
Purpose: Extensive evidence has suggested that risk factors of cancer development may also modulate cancer clinical outcome. Recent genome-wide association (GWA) studies identified several single nucleotide polymorphisms (SNPs) predisposing to colorectal cancer (CRC). Given the pivotal importance of these variants in CRC, we sought to evaluate their associations with clinical outcomes of the disease.Experimental Design: In a well-characterised cohort including 380 Chinese CRC patients, we genotyped seven SNPs identified in previous multi-stage GWA studies and analysed their associations with patient recurrence and survival.Results: One SNP on chromosome 15q13, rs4779584 was associated with reduced risk of death with a hazard ratio (HR) of 0.33 (95% confidence interval [CI] 0.15-0.72, P = 0.007). Another SNP in a gene-desert region on chromosome 10p14, rs10795668, was associated with a reduced risk of recurrence with an HR of 0.55 (95% CI 0.30-1.00, P = 0.05). In a stratified analysis, this association was only evident in patients receiving chemotherapy (HR = 0.32, 95% CI 0.14-0.78, P = 0.01, log rank P = 0.004), but not in those without chemotherapy (HR = 1.08, 95% CI 0.43-2.73, P = 0.87, log rank P = 0.66). Moreover, we found that the effects of chemotherapy on CRC recurrence was only evident in patients with the variant-containing genotypes (HR = 0.35, 95% CI 0.13-0.94, P = 0.04) but not in those with the wild-type genotype of rs10795668. Further analyses indicated a borderline significant interaction effect (P interaction = 0.05) between rs10795668 and chemotherapy on patient recurrence.Conclusions: Our data suggested that rs10795668, a CRC susceptibility variant identified by GWA studies, might be used as a biomarker to identify CRC patients with high risk of recurrence after chemotherapy. (C) 2011 Elsevier Ltd. All rights reserved.