FcγRⅡa和FcγRⅢa基因多态性与西妥昔单抗治疗转移性结直肠癌疗效相关性的Meta分析

    A Meta-Analysis of Associations between FcγRⅡa and FcγRⅢa Gene Polymorphisms and Cetuximab-Based Treatment Outcomes for Metastatic Colorectal Cancer

    • 摘要: 目的 系统评价FcγRⅡa和FcγRⅢa 基因多态性与西妥昔单抗为基础的药物在治疗转移性结直肠癌疗效的相关性。 方法 通过检索数据库,纳入2016年2月前所有符合纳入标准的有关FcγRⅡa和(或)FcγRⅢa基因多态性与西妥昔单抗在转移性结直肠癌中疗效的研究,采用Stata 11.0 软件进行Meta分析,用比值比及95%可信区间评价效应强度。 结果 共12篇文章符合纳入标准,累计1 016个病例。Meta分析的合并结果显示,FcγRⅡa和FcγRⅢa基因多态性与西妥昔单抗为基础的药物治疗在转移性结直肠癌患者的疗效无相关性。亚组分析结果显示,FcγRⅡa-H131R位点的突变型可增加西妥昔单抗在KRAS突变的转移性结直肠癌患者的疗效(RR vs. HH: 比值比2.395,95%可信区间1.522~3.771, I2=0.000; R vs. H: 比值比2.072,95%可信区间1.617~2.654, I2=0.457; HR+RR vs. HH: 比值比 3.067,95%可信区间1.582~5.944, I2=0.692; HR vs. HH: 比值比11.222,95%可信区间1.324~95.106, I2=0.769);FcγRⅢa-V158F的突变型可增加亚洲人群对西妥昔单抗的疗效(FF vs. VF+VV: 比值比1.534,95%可信区间1.138~2.069, I2=0.000; FF/VF: 比值比1.398,95%可信区间 1.040~1.879, I2=0.000)。 结论 FcγRⅡa和FcγRⅢa基因多态性与西妥昔单抗为基础的药物治疗在转移性结直肠癌中的疗效相关性可能存在种族差异和基因与基因的交互作用,需更多大样本高质量研究加以揭示。

       

      Abstract: Objective The purpose of this study is to evaluate the associations between FcγRⅡa and FcγRⅢa gene polymorphisms and Cetuximab-based treatment outcomes in metastatic colorectal cancer patients. Methods Eligible studies were searched from databases. Relative ratios (RR) with the corresponding 95% confidence interval (95%CI) were conducted. Statistical analysis was used with Stata 11.0. Results 12 articles were included, totally 1 016 cases. Pooled results indicated that no significant associations were found in FcγRⅡa and FcγRⅢa gene polymorphisms and Cetuximab-based treatment outcomes in metastatic colorectal cancer patients. In subgroup analysis, both KRAS and FcγRⅡa-H131R gene polymorphisms were significant association with Cetuximab-based treatment outcomes(RR vs. HH: RR=2.395,95%CI 1.522~3.771, I2=0.000; R vs. H: RR=2.072,95%CI 1.617~2.654, I2=0.457; HR+RR vs. HH: RR=3.067,95%CI 1.582~5.944, I2=0.692; HR vs. HH: RR=11.222,95%CI 1.324~95.106, I2=0.769), while FcγRⅢa-V158F gene polymorphism was seemed to be associated with treatment outcomes in Asian(FF vs. VF+VV: RR=1.534,95%CI 1.138~2.069, I2=0.000; FF/VF: RR=1.398,95%CI 1.040~1.879, I2=0.000). Conclusion FcγRⅡa and FcγRⅢa gene polymorphisms may be associated with Cetuximab-based treatment outcomes in metastatic colorectal cancer. Because racial differences and gene-to-gene interactions may influence such associations, more high-quality and large-scale studies are urgently needed.

       

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