Single Nucleotide Polymorphisms in Tobacco Metabolism and DNA Repair Genes and Prognosis in Resected Non-Small-Cell Lung Cancer
Single Nucleotide Polymorphisms in Tobacco Metabolism and DNA Repair Genes and Prognosis in Resected Non-Small-Cell Lung Cancer
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DOI：
10.1016/j.jss.2011.01.007
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发表时间：
2011-05-01
影响因子：
2.2
通讯作者：
Monzo, Mariano
中科院分区：
文献类型：
--
作者：
Campayo, Marc;Vinolas, Nuria;Monzo, Mariano
背景资料。如果与烟草相关的致癌物没有被灭活或从细胞中排出，它们可能会破坏DNA。参与烟草代谢、DNA修复和多药耐药的基因的单核苷酸多态(SNPs)与肺癌易感性有关。我们检测了其中10个基因的13个SNPs，并将结果与71例吸烟者或既往吸烟者切除的非小细胞肺癌(NSCLC)患者的进展时间(TTP)和总生存期(OS)相关联。从石蜡包埋的肿瘤中提取DNA。采用等位基因鉴别法对候选基因进行SNP分析。应用对数等级检验、Kaplan-Meier图和Cox多变量分析，评估TTP和生存率与所评估的SNPs的相关性。携带野生型(Wt)XPC rs2228001、wt CYP2C8 rs10509681或非wt Nat2 rs1799930的患者TTP较长。Wt ERCC1患者无明显延长TTP的趋势。未观察到SNPs与TTP之间的其他关系。在这四个基因中至少含有两种不利基因的患者，其TTP和OS比具有一种或没有任何一种不利基因的患者更短。在多变量分析中，非wt XPC rs2228001和至少两个不良基因的存在是TTP缩短的独立标记。烟草代谢和DNA修复基因中的SNPs可能影响
Background. If tobacco-related carcinogens are not inactivated or extruded from the cell, they can damage the DNA. Single nucleotide polymorphisms (SNPs) in genes involved in tobacco metabolism, DNA repair, and multidrug resistance have been related to lung cancer susceptibility. We examined 13 SNPs in 10 of these genes and correlated the results with time to progression (TTP) and overall survival (OS) in 71 smoker or former smoker patients with resected non-small-cell lung cancer (NSCLC).Materials and Methods. DNA was obtained from paraffin-embedded tumor. SNP analysis of the candidate genes was performed by allelic discrimination assay. Log-rank test, Kaplan-Meier plots, and Cox multivariate analysis were used to evaluate the association of TTP and survival with the SNPs evaluated.Results. Patients with wild-type (wt) XPC rs2228001, wt CYP2C8 rs10509681, or non-wt NAT2 rs1799930 had a longer TTP. Patients with wt ERCC1 showed a nonsignificant trend towards longer TTP. No other relation between SNPs and TTP were observed. Patients harboring at least two unfavorable genotypes in these four genes had a shorter TTP and OS than patients with either one or no unfavorable genotypes. In the multivariate analysis, non-wt XPC rs2228001 and the presence of at least two unfavorable genotypes emerged as independent markers for shorter TTP.Conclusions. SNPs in tobacco metabolism and DNA repair genes may influence