Methylenetetrahydrofolate reductase polymorphisms and risk of acute lymphoblastic leukemia-evidence from an updated meta-analysis including 35 studies.
Methylenetetrahydrofolate reductase polymorphisms and risk of acute lymphoblastic leukemia-evidence from an updated meta-analysis including 35 studies.
复制标题
DOI：
10.1186/1471-2350-13-77
复制
发表时间：
2012-09-04
影响因子：
--
通讯作者：
Mi W
中科院分区：
文献类型：
--
作者：
Wang H;Wang J;Zhao L;Liu X;Mi W
据报道，5，10-亚甲基四氢叶酸还原酶（MTHFR）变体C677 T和A1298 C与急性淋巴细胞白血病（ALL）风险降低相关。然而，从个别动力不足的研究得出的结果是相互矛盾的。我们对MTHFR多态性与ALL风险之间的关系进行了最新的荟萃分析。通过PUBMED和EMBASE数据库检索相关出版物。采用比值比（OR）分析MTHFR C677 T和A1298 C多态性与ALL发病风险的关系。估计异质性和发表偏倚。进行Meta回归分析，以评估异质性的潜在来源。C677 T多态性与ALL风险降低相关（等位基因对比：ORRE = 0.91，95%CI：0.83-0.99）。亚组分析显示MTHFR C677 T变异与儿童和白人ALL易感性降低相关。Meta回归分析显示T等位基因与ALL相关性的logOR随病例组男/女比例的增加而增加（P = 0.01）。关于A1298 C多态性，未观察到显著关联（等位基因对比：ORRE = 1.01，95%CI：0.91-1.11）。C677 T或A1298 C多态性无发表偏倚。本荟萃分析提示MTHFR基因C677 T多态性而非A1298 C多态性与ALL风险降低相关，尤其是在儿童和白人受试者中。我们的研究结果表明，C677 T多态性对ALL易感性的影响是修改的性别比例的情况下（M/F）。由于叶酸摄入量可能是一个可能的混杂因素，在未来的前瞻性研究中包括这一因素是必要的。进一步的荟萃分析研究至少应根据叶酸水平和性别进行分层，以提供更有力和更有信息量的结果。
5,10-methylenetetrahydrofolate reductase (MTHFR) variants, C677T and A1298C, have been reported to be associated with decreased risk of acute lymphoblastic leukemia (ALL). However, results derived from individually underpowered studies are conflicting. We carried out an updated meta-analysis on the association between MTHFR polymorphisms and ALL risk. Relevant publications were searched through PUBMED and EMBASE databases. The associations between MTHFR C677T and A1298C polymorphisms and the risk of ALL were evaluated by odds ratios (ORs). The heterogeneity and publication bias were estimated. Meta-regression analysis was performed to evaluate the potential sources of heterogeneity. C677T polymorphism was associated with a reduced risk of ALL (allele contrast: ORRE = 0.91, 95% CI: 0.83-0.99). Subgroup analysis showed MTHFR C677T variant was associated with decreased susceptibility to ALL in children and Caucasians. Meta-regression showed the logOR for the association between T allele and ALL increased as sex ratio (M/F) in the case group increased (P = 0.01). Regarding A1298C polymorphism, no significant association was observed (allele contrast: ORRE = 1.01, 95% CI: 0.91-1.11). There was no publication bias for C677T or A1298C polymorphism. The present meta-analysis suggests that the C677T polymorphism, not A1298C, in MTHFR gene is associated with a decreased risk of ALL, particularly among children and Caucasians subjects. Our findings suggest that the influence of the C677T polymorphism on ALL susceptibility is modified by sex ratio in cases (M/F). Since folate intake may be a possible confounding factor, including this factor in future prospective studies is warranted. Further meta-analysis studies should be at least stratified for folate levels and gender to give more powerful and informative results.