胃肠癌MTHFR基因C677T多态性与5-氟尿嘧啶化疗方案治疗敏感性的相关性Meta分析

Association between MTHFR C677T polymorphism and susceptibility of 5-FU chemotherapy regimens in the treatment of gastrointestinal cancer: a Meta-analysis

目的 :系统评价胃肠癌组织中亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)基因C677T位点多态性与含5-氟尿嘧啶化疗方案治疗敏感性的相关性。方法:系统检索PubMed、EBSCO、Web of Science、Cochrane Library、中国生物医学文献数据库、中国知网、维普以及万方数据库,收集有关MTHFR C677T基因多态性与含5-氟尿嘧啶化疗方案治疗胃肠癌敏感性关系的研究文献,检索时限均从各数据库建库至2016年12月。由2位评价者按照纳入与排除标准独立筛选文献、提取资料后,采用Rev Man 5.3软件进行Meta分析,并采用STATA 12.0统计学软件进行敏感性分析和发表偏倚评估。结果:共纳入11项研究,共1 267例胃肠癌患者。携带T等位基因的患者对含5-氟尿嘧啶化疗方案的敏感性明显高于携带C等位基因的患者[比值比(odds ratio,OR)=5.31,95%可信区间(confidence interval,CI)为3.23~8.73,P<0.001]。TT基因型患者对化疗方案的敏感性明显高于CC基因型患者(OR=4.87,95%CI为2.18~10.86,P<0.001)。TT+TC基因型患者对化疗方案的敏感性明显高于CC基因型患者(OR=0.52,95%CI为0.33~0.84,P=0.007)。TT基因型患者对化疗方案的敏感性明显高于CC+TC基因型患者(OR=4.39,95%CI为2.07~9.32,P<0.001)。结论:胃肠癌患者的MTHFR C677T基因多态性与含5-氟尿嘧啶化疗方案治疗敏感性明显相关。

Objective： To systematically evaluate the association between methylenetetrahydrofolate reductase （MTHFR） C677T gene polymorphism and the sensitivity of 5-fluorouracil （5-FU） chemotherapy regimens in the treatment of gastrointestinal cancer. Methods： Such databases as PubMed,EBSCO,Web of Science,Cochrane Library,Chinese BioMedical Literature Database （CBM）,China National Knowledge Infrastructure （CNKI）,VIP and WanFang Data were systematically searched to collect studies on the association between MTHFR C677T gene polymorphism and the sensitivity of 5-FU chemotherapy regimens in the treatment of gastrointestinal cancer published from each database establishing time to December 2016.All of subjects were selected by two reviewers,and the data were extracted according to the inclusion and exclusion criteria.Meta-analysis was performed using RevMan 5.3 statistical software,the sensitivity analysis and publication bias assessment were performed using STATA 12.0 statistical software. Results： A total of 11 studies involving 1 267 patients with gastrointestinal cancer were included.The sensitivity of patients with MTHFR 677T allele to 5-FU chemotherapy regimens was significantly higher than that of patients with C allele[odds ratio （OR）=5.31,95% confidence interval （CI）：3.23-8.73,P 〈 0.001].The sensitivity of patients carried TT allele to chemotherapy regimens was significantly higher than that of patients carried CC allele （OR=4.87,95%CI：2.18-10.86,P 〈 0.001）.The sensitivity of patients with TT＋TC genotype to chemotherapy regimens was significantly higher than that of patients with CC genotype （OR=0.52,95%CI：0.33-0.84,P=0.007）.TT genotype patients were significantly more sensitive to chemotherapy as compared with CC＋TC genotype patients （OR=4.39,95%CI：2.07-9.32,P 〈 0.001）. Conclusion： The polymorphism of MTHFR C677T gene in gastrointestinal cancer patients is significantly correlated with the sensitivity of 5-FU chemotherapy regimen.