National Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Changhai Hospital of Shanghai, Shanghai, China.
Clin Cancer Res. 2012 Jul 15;18(14):3972-81. doi: 10.1158/1078-0432.CCR-11-1531. Epub 2012 Jun 15.
Published data have shown conflicting results about the relationship between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms (Arg399Gln and Arg194Trp) and clinical outcome of platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis is needed to provide a systematic review of the published findings.
We conducted a systematic review and meta-analysis to evaluate the predictive value of XRCC1 gene polymorphisms on clinical outcome up to October 1, 2010. The quality of each study was scored on the basis of predefined criteria.
A total of 13 eligible follow-up studies met all the inclusion criteria. The XRCC1194Trp allele was found to be significantly associated with a favorable response rate relative to 194Arg [Trp vs. Arg: OR, 1.88; 95% confidence interval (CI), 1.48-2.38]. XRCC1399Gln was less favorably associated with both response rate (Gln vs. Arg: OR, 0.67; 95% CI, 0.52-0.87) and overall survival (Gln vs. Arg: HR, 1.30; 95% CI, 1.04-1.63) than 399Arg in analyses using all available studies; but these associations became insignificant when only high-quality studies were used.
These findings suggest a predictive role for XRCC1 gene polymorphisms in clinical outcome. However, the role of 399Gln could be considered controversial because its impact on clinical outcome was insignificant in high-quality studies. These findings show the importance of establishing suitable criteria, including genetic epidemiologic, phenotypic, and clinical criteria, to improve quality control of study design and methods in pharmacogenomic studies related to XRCC1 gene polymorphism.
已发表的数据显示，X 射线修复交叉互补基因 1（XRCC1）基因多态性（Arg399Gln 和 Arg194Trp）与晚期非小细胞肺癌（NSCLC）患者铂类化疗的临床结果之间的关系存在矛盾的结果。需要进行荟萃分析以系统地回顾已发表的研究结果。
我们进行了系统的回顾和荟萃分析，以评估截至 2010 年 10 月 1 日，XRCC1 基因多态性对临床结果的预测价值。根据预先确定的标准对每项研究的质量进行评分。
共有 13 项符合所有纳入标准的随访研究。与 194Arg 相比，XRCC1194Trp 等位基因与有利的反应率显著相关[Trp 与 Arg：OR，1.88；95%置信区间（CI），1.48-2.38]。与 399Arg 相比，XRCC1399Gln 与反应率（Gln 与 Arg：OR，0.67；95%CI，0.52-0.87）和总生存率（Gln 与 Arg：HR，1.30；95%CI，1.04-1.63）的相关性较差，在使用所有可用研究的分析中；但是当仅使用高质量的研究时，这些相关性变得不显著。
这些发现表明 XRCC1 基因多态性在临床结果中具有预测作用。然而，399Gln 的作用可能被认为有争议，因为其对临床结果的影响在高质量的研究中并不显著。这些发现表明建立适当的标准（包括遗传流行病学，表型和临床标准）的重要性，以改善与 XRCC1 基因多态性相关的药物基因组学研究的研究设计和方法的质量控制。
