Objective: Single nucleotide polymorphisms ( SNPs) in DNA repair genes are believed to be associated with the survival of lung cancer patients because of their effects on the DNA repair capacity. This work aimed to define the role of DNA repair gene SNPs in non-small cell lung cancer ( NSCLC ) patients, and investigate the association of lung cancer survival with SNPs of x-ray repair cross-complementing group 1 ( XRCCI ) and human 8-oxoguaninc glycosylasel ( hOGGl). Methods: The Taqman SNP method was used to detect SNPs in XRCC1 (rs 25487) and hOGGl (rs 1052133) genes, and evaluate their association with the overall survival of 420 Chinese patients with king cancer. The association of lung cancer survival with genetic polymorphisms were evaluated by the Kaplan-Meier method and iog-rank test. The Cox regression, model wras used to calculate the adjusted hazard ratio. Results: Advanced cancer stage and advanced age were independently associated with the overall survival of lung cancer patients ( P = 1.000E-4 andF= 3.828E-11 ), respectively. XRCCI and hGGGl polymorphisms were not statistically associated with lung cancer survival in the total population studied. After stratification by smoking status and smoking amount, individuals with the hGGGl mutant G genotype had a higher hazard ratio of death than those with the hGGGl wild CC genotype in light smokers (log-rank P = 0.021 3, HR = 8.24). However, no association was found in nonsmokers and heavy smokers. Conclusion: To our knowledge, this is the first study to reveal the prognostic roles of the hOGGl G genotype in the survival of Chinese NSCLC patients and patients with, different smoking statuses. The data indicated that the hOGGl G genotype was associated with lung cancer survival in light smokers. Large and well-designed studies with diverse populations and functional evaluations are warranted to confirm these findings.%目的:DNA损伤修复作为维持体内基因稳定性和修复 DNA损伤的重要机制,在肿瘤的发生、发展、转归及预后中发挥 重要作用,DNA损伤修复基因多态性通过影响 DNA损伤修复能力进而影响肿瘤患者生存.本研究旨在探讨 DNA损伤修复基因 XRCC1、hOGG1多态性对肺癌患者生存的影响.方法:收集 420例原发性非小细胞肺癌病例,采用 TaqMan SNP技术检测肺癌患 者外周血 DNA XRCC1(rs25487)和 hOGG1(rs1052133)多态性.采用 Kaplan-Meier 法分析生存情况,Log-rank 法进行单因素检 验,Cox 回归用来计算调整混杂因素的风险比(Hazard Ratio,HR).结果:患者临床特征和预后风险的分析显示,年龄≥60岁和病 理分期晚期(Ⅲ/Ⅳ期)是影响肺癌预后的独立危险因素,P值分别为 1.000E-4和 3.828E-11.DNA修复基因 XRCC1和 hOGG1多 态性与肺癌患者生存情况的分析未见不同基因型的生存曲线的分布具有统计学差异.按照吸烟情况分层后,在轻度吸烟者(吸 烟量<40包/年)中,携带 hOGG1突变型 G等位基因较携带野生型 C基因型生存率低(P=0.021 3),经 Cox回归分析显示携带 G等位 基因的患者死亡风险为野生型的 8.24倍.而在非吸烟者和重度吸烟者中未见多态性对患者生存的影响.结论:本研究首次发现 碱基切除修复通路基因 hOGG1 rs1052133多态性对肺癌患者生存存在一定影响,尤其是在轻度吸烟者中,携带突变型等位基因增 大肺癌患者死亡风险,相关机制有待进一步大规模样本验证.
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