Email updates

Keep up to date with the latest news and content from BMC Medical Genetics and BioMed Central.

Open Access Research article

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

Haigang Wang12, Jiali Wang3, Lixia Zhao24, Xinchun Liu1* and Wenjie Mi1*

Author Affiliations

1 Pharmacy Intravenous Admixture Services, Qilu Hospital, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, China

2 College of Pharmacy, Shandong University, Jinan, China

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

4 Department of Pharmacy, Qilu Hospital, Shandong University, Jinan, China

For all author emails, please log on.

BMC Medical Genetics 2012, 13:77  doi:10.1186/1471-2350-13-77

Published: 4 September 2012

Abstract

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: 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.

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.

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