Differential effects of the methylenetetrahydrofolate reductase polymorphisms (C677T and A1298C) on hematological malignancies among Latinos: a meta-analysis

Abstract Our objective was to determine the association between the methylenetetrahydrofolate reductase polymorphisms (C677T and A1298C) and the risk of developing acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), acute myeloid leukemia (AML), and multiple myelomas (MM) in Latinos. PubMed, SCOPUS, EBSCO, LILACS, and other Latin-specific databases were searched for case-control studies that investigated the association between these polymorphisms and hematologic malignancies until November 2017. Genotype distributions were extracted and either fixed-effects or random-effects models were used to calculate the pooled crude odds ratios (ORs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. No publication bias was detected by the Begg-Mazumdar’s test and Egger’s test. From 290 publications, we identified 15 studies on the C677T polymorphism and 13 studies on the A1298C polymorphism. We observed a significant decrease in risk for the C677T polymorphism (OR range=0.54-0.75, p<0.01) and a significant increase in risk for the A1298C polymorphism (OR range=1.28-2.52, p<0.05) in developing ALL for all genetic models. No associations were determined for CML, AML, or MM for either polymorphism. This meta-analysis demonstrated that the A1298C polymorphism was associated with an increased risk of developing ALL, whereas the C677T polymorphism was associated with a decreased risk (protective factor) in the Latino population.

摘要 本研究旨在探讨拉丁裔人群中亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase）基因多态性（C677T与A1298C）与急性淋巴细胞白血病（ALL）、慢性髓系白血病（CML）、急性髓系白血病（AML）及多发性骨髓瘤（MM）发病风险的关联。我们检索了PubMed、SCOPUS、EBSCO、LILACS及其他拉美专属数据库中截至2017年11月发表的、探讨上述基因多态性与血液系统恶性肿瘤关联的病例对照研究。提取纳入研究的基因型分布数据，采用固定效应模型或随机效应模型计算杂合子、纯合子、显性遗传、隐性遗传及等位基因遗传模型下的合并粗比值比（OR）。经Begg-Mazumdar检验与Egger检验，未检测到发表偏倚。从290篇初始文献中，最终纳入15项针对C677T多态性的研究及13项针对A1298C多态性的研究。针对所有遗传模型，C677T多态性可显著降低急性淋巴细胞白血病的发病风险（OR范围0.54~0.75，p<0.01）；而A1298C多态性则显著升高该疾病的发病风险（OR范围1.28~2.52，p<0.05）。两种基因多态性均与慢性髓系白血病、急性髓系白血病及多发性骨髓瘤的发病风险无显著关联。本荟萃分析结果显示，在拉丁裔人群中，A1298C多态性与急性淋巴细胞白血病发病风险升高相关，而C677T多态性则与该疾病发病风险降低（即保护因素）相关。