Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia-Evidence from an updated meta-analysis including 35 studies

BMC Medical Genetics

Wenjie Mi²  Xinchun Liu²  Lixia Zhao¹  Jiali Wang³  Haigang Wang⁴ 

[1]Department of Pharmacy, Qilu Hospital, Shandong University, Jinan, China

[2]Pharmacy Intravenous Admixture Services, Qilu Hospital, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, China

[3]Department of Emergency, Qilu Hospital, Shandong University, Jinan, China

[4]College of Pharmacy, Shandong University, Jinan, China

关键词: Update;    5,10-methylenetetrahydrofolate reductase;    Meta-analysis;    Polymorphism;    Acute lymphoblastic leukemia;   

Others  :  1177807
DOI  :  10.1186/1471-2350-13-77

 received in 2011-10-31, accepted in 2012-08-27,  发布年份 2012

【 摘 要 】

Background

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.

Methods

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.

Results

C677T polymorphism was associated with a reduced risk of ALL (allele contrast: OR_RE = 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: OR_RE = 1.01, 95% CI: 0.91-1.11). There was no publication bias for C677T or A1298C polymorphism.

Conclusions

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.

【 授权许可】

   
2012 Wang et al.; licensee BioMed Central Ltd.

【 图 表 】

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