China Medical University, Shenyang 110001, PR China.
BMC Cancer. 2012 Feb 17;12:71. doi: 10.1186/1471-2407-12-71.
X-ray repair cross-complementing group 1 (XRCC1) protein plays an important role in the repair of DNA damage and adducts. Single nucleotide polymorphisms (SNPs) of XRCC1 are suspected to have some relationship with response to chemotherapy and overall survival of lung cancer. This meta-analysis aimed to summarize published data on the association between the commonest SNPs of XRCC1 (Arg194Trp, C > T, rs1799782 and Arg399Gln, G > A, rs25487) and clinical outcome of lung cancer patients.
We retrieved the relevant articles from PubMed, EMBASE and the China National Knowledge Infrastructure (CNKI) databases. Studies were selected using specific inclusion and exclusion criteria. Primary outcomes included objective response (i.e., complete response + partial response vs. progressive disease + stable disease) and overall survival (OS). Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were estimated. All analyses were performed using the Stata software.
Twenty-two articles were included in the present analysis. XRCC1 Arg194Trp and Arg399Gln polymorphisms were significantly associated with response to treatment in lung cancer patients. Patients with C/T genotype, T/T genotype and minor variant T allele at Arg194Trp were more likely to respond to platinum-based chemotherapy compared with those with C/C genotype (C/T vs. C/C: OR, 2.54; 95%CI, 1.95-3.31; T/T vs. C/C: OR, 2.06; 95%CI, 1.39-3.06; C/T+T/T vs. C/C: OR, 2.42; 95% CI, 1.88-3.10). For XRCC1 Arg399Gln, G/A genotype, A/A genotype and minor variant A allele were associated with objective response in all patients (G/A vs. G/G: OR, 0.67; 95%CI, 0.50-0.90; A/A vs. G/G: OR, 0.43; 95%CI, 0.25-0.73; A/A+G/A vs. G/G: OR, 0.63; 95%CI, 0.49-0.83). Both G/A and A/A genotypes of XRCC1 Arg399Gln could influence overall survival of lung cancer patients (G/A vs. G/G: HR, 1.23; 95%CI, 1.06-1.44; A/A vs. G/G: HR, 2.03; 95%CI, 1.20-3.45). Interaction analysis suggested that compared with the patients carrying C/T+T/T genotype at XRCC1 194 and G/G genotype at XRCC1 399, the patients carrying 194 C/C and 399 G/A+A/A or 194 C/C and 399 G/G genotype showed much worse objective response.
Genetic polymorphisms in XRCC1 gene might be associated with overall survival and response to platinum-based chemotherapy in lung cancer patients.
X 射线修复交叉互补基因 1（XRCC1）蛋白在 DNA 损伤和加合物的修复中起着重要作用。XRCC1 的单核苷酸多态性（SNP）被怀疑与肺癌的化疗反应和总生存期有关。本荟萃分析旨在总结 XRCC1 常见 SNP（Arg194Trp、C>T，rs1799782 和 Arg399Gln、G>A，rs25487）与肺癌患者临床结局的相关研究数据。
我们从 PubMed、EMBASE 和中国国家知识基础设施（CNKI）数据库中检索相关文章。使用特定的纳入和排除标准选择研究。主要结局包括客观缓解（即完全缓解+部分缓解与进展性疾病+稳定疾病）和总生存期（OS）。使用 95%置信区间（CI）的比值比（OR）或风险比（HR）进行估计。所有分析均使用 Stata 软件进行。
本分析共纳入 22 篇文章。XRCC1 Arg194Trp 和 Arg399Gln 多态性与肺癌患者对治疗的反应显著相关。与 Arg194Trp 的 C/C 基因型相比，携带 C/T 基因型、T/T 基因型和 T 等位基因的患者更有可能对铂类化疗有反应（C/T 与 C/C：OR，2.54；95%CI，1.95-3.31；T/T 与 C/C：OR，2.06；95%CI，1.39-3.06；C/T+T/T 与 C/C：OR，2.42；95%CI，1.88-3.10）。对于 XRCC1 Arg399Gln，G/A 基因型、A/A 基因型和 A 等位基因与所有患者的客观缓解相关（G/A 与 G/G：OR，0.67；95%CI，0.50-0.90；A/A 与 G/G：OR，0.43；95%CI，0.25-0.73；A/A+G/A 与 G/G：OR，0.63；95%CI，0.49-0.83）。XRCC1 Arg399Gln 的 G/A 和 A/A 基因型均能影响肺癌患者的总生存期（G/A 与 G/G：HR，1.23；95%CI，1.06-1.44；A/A 与 G/G：HR，2.03；95%CI，1.20-3.45）。交互分析表明，与携带 XRCC1 194 C/T+T/T 基因型和 XRCC1 399 G/G 基因型的患者相比，携带 XRCC1 194 C/C 和 XRCC1 399 G/A+A/A 或 C/C 和 G/G 基因型的患者客观缓解更差。
XRCC1 基因的遗传多态性可能与肺癌患者的总生存期和铂类化疗反应有关。
