Genetic Polymorphism of DNA Base-excision Repair Genes (APE1, OGG1 and XRCC1) and Their Correlation with Risk of Lung Cancer in a Chinese Population
Genetic Polymorphism of DNA Base-excision Repair Genes (APE1, OGG1 and XRCC1) and Their Correlation with Risk of Lung Cancer in a Chinese Population
复制标题
中国人群DNA碱基切除修复基因（APE1、OGG1和XRCC1）的遗传多态性及其与肺癌风险的相关性。
DOI：
10.1016/j.arcmed.2011.04.005
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发表时间：
2011-04-01
影响因子：
7.7
通讯作者：
Wang, Dong
中科院分区：
文献类型：
--
作者：
Li, Zheng;Guan, Wei;Wang, Dong
背景和目标。活性氧（ROS）和许多致癌物质可能会导致DNA损伤，包括导致肺癌风险的氧化性碱基损伤。碱基切除修复（BER）途径可以有效地清除氧化损伤，其中8-氧代鸟嘌呤糖基化酶-1（OGG 1）、X射线修复交叉互补1（XRCC 1）和脱嘌呤/脱嘧啶核酸内切酶1（APE 1）发挥关键作用。本研究的目的是分析DNA BER基因（OOG 1、XRCC 1和APE 1）的多态性，并探讨其与肺癌的关系以及这些变异的联合作用。采用病例对照研究方法，对455例肺癌患者和443例非肺癌患者进行OGG 1（Ser 326 Cys）、XRCC 1（Arg 399 Gln）、APE 1（Asp 148 Glu和-141T/G）基因多态性分析，并采用多因素Logistic回归模型分析其与肺癌发病风险的相关性。变体APE 1 - 141 GG纯合子个体显示出对肺癌总体（OR = 0.62; 95% CI：0.42-0.91; p = 0.02）和肺腺癌（OR = 0.65; 95% CI，0.44-0.96; p = 0.03）的保护作用。当分析变异等位基因的组合效应时，鉴定了84名患者和对照，他们对于两个或三个潜在的保护性等位基因是纯合的（即，OGGl 326Cys、XRCCl 399Gln和APE 1 - 141G）。当所有患者均进行分析时，OR显著降低（OR = 0.62; 95%CI：0.38-0.99; p = 0.05）。BER基因多态性的联合作用可能与肺癌的发生有关。(C)2011年IMSS。爱思唯尔公司出版
Background and Aims. Reactive oxygen species (ROS) and numerous carcinogens may cause DNA damage including oxidative base lesions that contribute to the risk of lung cancer. The base excision repair (BER) pathway could effectively remove oxidative lesions in which 8-oxoguanine glycosylase-1 (OGG1), x-ray repair cross-complementing 1 (XRCC1), and apurinic/apyimidinic endonuclease 1 (APE1) play key roles. The aim of this study was to analyze the polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of lung cancer.Methods. In a hospital-based, case-control study of 455 lung cancer cases and 443 cancer-free hospital controls, the SNPs of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), APE1 (Asp148Glu and -141T/G) were genotyped and analyzed for their correlation with the risk of lung cancer in multivariate logistic regression models.Results. Individuals homozygous for the variants APE1 -141GG showed a protective effect for lung cancer overall (OR = 0.62; 95% CI: 0.42-0.91; p = 0.02) and for lung adenocarcinoma (OR = 0.65; 95% CI, 0.44-0.96; p = 0.03). When analyzing the combined effects of variant alleles, 84 patients and controls were identified who were homozygous for two or three of the potential protective alleles (i.e., OGG1 326Cys, XRCC1 399Gln and APE1 -141G). ORs were significantly reduced when all patients were analyzed (OR = 0.62; 95% CI: 0.38-0.99; p = 0.05).Conclusions. The combined effects of polymorphisms within BER genes may contribute to the tumorigenesis of lung cancer. (C) 2011 IMSS. Published by Elsevier Inc.