Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, China.
Mol Biol Rep. 2012 Oct;39(10):9535-47. doi: 10.1007/s11033-012-1818-2. Epub 2012 Jun 23.
X-ray repair cross-complementing group 1 gene (XRCC1) has been implicated in risk for lung cancer. However, the results from different studies remain controversial. In this meta-analysis, we have assessed 44 published case-control studies regarding associations of lung cancer risk with three common polymorphisms, codon 194, codon 280 and codon 399, and -77 T > C in the promoter region of XRCC1. The results in total population showed that the risk for lung cancer was increased among the variant homozygote Trp/Trp of codon 194 polymorphism, compared with the wild type Arg/Arg (OR: 1.19; 95 % CI 1.01-1.39), and the variant genotype CC of -77 T > C polymorphism showed a significantly increased risk of developing lung cancer, compared to wild-type genotype TT (OR: 1.91; 95 % CI 1.24-2.94). However, no associations were found between lung cancer risk and codon 280, codon 399. In the subgroup analyses by ethnicity, the OR for the variant homozygote Trp/Trp of codon 194 was 1.21(95 % CI 1.02-1.43) for Asian. When stratified by source of control, we found a protective effect of codon 194 Arg/Trp genotype (OR: 0.87; 95 % CI 0.77-0.98) and risk effect of codon 399 combined Arg/Gln + Gln/Gln variant genotype (OR: 1.09; 95 % CI 1.01-1.18) for lung cancer on the basis of hospital control. Subgroup analyses by histological types of lung cancer indicated that the heterozygote Arg/Trp in codon 194 could decrease and the combined variant genotype Arg/Gln + Gln/Gln in codon 399 could increase the risk of non-small cell lung cancer (OR: 0.69; 95 % CI 0.57-0.85 and OR: 1.14; 95 % CI 1.04-1.24). In conclusion, this meta-analysis has demonstrated that codon 194, codon 399 and -77 T > C polymorphisms of XRCC1 gene might have contributed to individual susceptibility to lung cancer. To further evaluate effect of XRCC1 polymorphisms, gene-gene interaction and gene-environment interaction on lung cancer risk, a single large sample size study with thousands of subjects is required to get conclusive results.
X 射线修复交叉互补基因 1 （XRCC1）已被认为与肺癌风险有关。然而，来自不同研究的结果仍存在争议。在这项荟萃分析中，我们评估了 44 项已发表的病例对照研究，探讨了 XRCC1 中三个常见的多态性（密码子 194、密码子 280 和密码子 399）以及启动子区域的 -77T > C 与肺癌风险之间的关联。总体人群的结果表明，与野生型 Arg/Arg（OR：1.19；95%CI：1.01-1.39）相比，密码子 194 中的变体纯合子 Trp/Trp 发生肺癌的风险增加，而 -77T > C 多态性的变体基因型 CC 发生肺癌的风险显著增加，与野生型基因型 TT 相比（OR：1.91；95%CI：1.24-2.94）。然而，未发现密码子 280、密码子 399 与肺癌风险之间存在关联。按种族进行亚组分析时，亚洲人群中密码子 194 的变体纯合子 Trp/Trp 的 OR 为 1.21（95%CI：1.02-1.43）。按对照来源分层时，我们发现密码子 194Arg/Trp 基因型（OR：0.87；95%CI：0.77-0.98）具有保护作用，密码子 399 联合 Arg/Gln + Gln/Gln 变体基因型（OR：1.09；95%CI：1.01-1.18）具有风险作用，这两种基因型都与基于医院对照的肺癌有关。按肺癌的组织学类型进行的亚组分析表明，密码子 194 的杂合子 Arg/Trp 可以降低风险，而密码子 399 中的联合变体基因型 Arg/Gln + Gln/Gln 可以增加非小细胞肺癌的风险（OR：0.69；95%CI：0.57-0.85 和 OR：1.14；95%CI：1.04-1.24）。总之，这项荟萃分析表明，XRCC1 基因的密码子 194、密码子 399 和 -77T > C 多态性可能导致个体易患肺癌。为了进一步评估 XRCC1 多态性、基因-基因相互作用和基因-环境相互作用对肺癌风险的影响，需要进行一项具有数千名受试者的大型单一样本量研究，以得出明确的结论。
