胸苷酸合成酶基因多态性与儿童急性淋巴细胞白血病风险的Meta分析

Meta-analysis of Thymidylate Synthase Gene Polymorphism and Childhood Acute Lymphoblastic Leukemia Risk

目的综合评价胸苷酸合成酶(TS)基因del6多态性与儿童急性淋巴细胞白血病(ALL)易感性的关系。方法系统检索Pubmed、Science Direct、Google Scholar、中国知网(CNKI)和万方数据库,获取有关TS基因del6多态性与儿童ALL发生风险的文献资料,评估纳入研究的方法学质量并提取相关数据。以比值比(OR)和95%可信区间(CI)作为效应指标评估关联强度,纳入研究之间的异质性检验和合并OR值计算采用Revman 5.3软件,发表性偏倚应用漏斗图评估。结果共纳入6个病例-对照研究,包括ALL患儿2104例,对照2320例。Meta分析结果显示,在整体人群比较中4种遗传模型均未发现TS基因del6多态性与儿童ALL易感性有显著性关联(杂合子模型:OR=0.99,95%CI:0.85~1.15,P=0.87;纯合子模型:OR=1.11,95%CI:0.90~1.38,P=0.33;隐性模型:OR=0.97,95%CI:0.76~1.25,P=0.84;显性模型:OR=1.01,95%CI:0.88~1.17,P=0.86);根据种族进行分层分析也未发现显著性关联。漏斗图未检测到显著性发表性偏倚,敏感度分析表明合并结果是稳健可靠的。结论目前的Meta分析表明TS基因del6多态性与儿童ALL易感性无关联。

Objective To evaluate synthetically the association of thymidylate synthase（TS） gene del6 polymorphism with susceptibility to develop childhood acute lymphoblastic leukemia（ALL）. Methods The Pubmed, Science Direct, Google Scholar, China National Knowledge Infrastructure and Wanfang databases were systematically searched to obtain the literatures about the association between TS del6 polymorphism and childhood ALL risk. The methodological quality of the included studies was assessed and relevant data were extracted. Odds ratios（OR） with 95% confidence intervals（CI） were applied to evaluate the strength of association. The heterogeneity test and combined ORs calculation of the included studies were performed by using Revman 5.3 software. The funnel plot was used to assess publication bias. Results Six case-control studies bearing 2104 children with ALL and 2320 controls were finally included in the meta-analysis. The combined results suggested that there was no significant association between TS del6 polymorphism and susceptibility to childhood ALL in overall comparisons under four genetic models（Heterozygote model：OR=0.99, 95% CI：0.85-1.15, P=0.87; Homozygote model：OR=1.11, 95% CI：0.90-1.38, P=0.33; Recessive model：OR=0.97, 95% CI：0.76-1.25, P=0.84; Dominant model：OR=1.01, 95% CI：0.88-1.17, P=0.86）. No significant association was found in the stratification analysis according to ethnicity. No significant publication bias was detected by funnel plot and sensitivity analysis suggested robustness and credibility of the results. Conclusion The present meta-analysis suggested that TS del6 polymorphism was not associated with the susceptibility to childhood ALL.