meta分析教程

Leukemia Research 34 (2010) 1596–1600

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Leukemia

Research

j o u r n a l h o m e p a g e :w w w.e l s e v i e r.c o m /l o c a t e /l e u k r e

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MTHFR C677T polymorphisms and childhood acute lymphoblastic leukemia:A meta-analysis

Jing Wang a ,Ping Zhan b ,Bing Chen a ,Rongfu Zhou a ,Yonggong Yang a ,Jian Ouyang a ,∗

a Department of Hematology,the Affiliated DrumTower Hospital of Nanjing University Medical School,321Zhongshan Road,Nanjing 210008,Jiangsu PR China b

Department of Respiratory Medicine,Nanjing Chest Hospital,Nanjing,PR China

a r t i c l e i n f o Article history:

Received 4January 2010

Received in revised form 19March 2010Accepted 20March 2010

Available online 20 April 2010Keywords:

MTHFR polymorphisms

Acute lymphoblastic leukemia Meta-analysis

a b s t r a c t

To date,case–control studies on the association between methylenetetrahydrofolate reductase (MTHFR)C677T and childhood acute lymphoblastic leukemia have provided either controversial or inconclusive results.To clarify the effect of MTHFR C677T on the risk of childhood acute lymphoblastic leukemia,a meta-analysis of all case–control observational studies was performed.Heterogeneity (I 2=65%,P <0.0001)for C677T among the studies was extreme.The random effects (RE)model showed that the 677T allele was not associated with a decreased susceptibility risk of childhood acute lymphoblastic leukemia compared with the C allele [OR =0.96,95%confidence interval (CI)(0.88–1.04),P =0.34].The contrast of homozygotes,recessive model and dominant model produced the same pattern of results as the allele contrast.Although MTHFR C677T was associated with increased risks of colorectal cancer,leukemia,and gastric cancer,our pooled data suggest no evidence for a major role of MTHFR C677T in the carcinogenesis of childhood acute lymphoblastic leukemia.

© 2010 Elsevier Ltd. All rights reserved.

1.Introduction

Acute lymphoblastic leukemia (ALL)is the most common malig-nancy affecting children,constituting about 30%of all cancers among children [1,2].Although significant improvements in both ALL diagnosis and treatment have been made over the past decades,the etiology of most cases of ALL remains unknown due to proba-ble multifactorial mechanisms of pathogenesis [3].Pediatric acute leukemias are likely influenced by both the genetic background and the environment of the patient [4,5].

Methylenetetrahydrofolate reductase (MTHFR)plays an important role in folate metabolism by catalyzing the irre-versible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate [4].A common polymorphism at the nucleotide 677,C677T (Ala →Val),in the gene for the enzyme MTHFR,results in a less stable version of the enzyme [6].MTHFR C677T has been associated with an increased risk of colorectal cancer,leukemia,and gastric cancer [7].The role of MTHFR polymorphisms in the development of childhood ALL has been investigated in the past decade,with conflicting results.Sev-eral studies have previously suggested an association between the MTHFR C677T polymorphism and a decreased risk of acute lymphoblastic leukemia (ALL)[8,9].However,other studies have

∗Corresponding author.Tel.:+862583105211;fax:+862583105211.E-mail address:ouyang211@ (J.Ouyang).failed to confirm such an association [10,11].Moreover,two meta-analyses [12,13]investigating the same hypothesis,quite similar in methods and performed almost at the same time,yielded different conclusions.The exact relationship between genetic polymorphisms of MTHFR C677T and susceptibility to childhood ALL has not been entirely established.To clarify the effect of MTHFR C677T on the risk of childhood ALL,our study undertakes a meta-analysis of all published case–control observational studies.

2.Methods

2.1.Publication search

The electronic databases PubMed,Embase,Web of Science,and CNKI (China National Knowledge Infrastructure)were searched for studies to include in the present meta-analysis,using the terms:“Methylenetetrahydrofolate Reductase,”“genotype,”“Leuk(a)emia,”“Acute lymphocytic,”“Acute lymphoblastic,”“Child-hood,”“P(a)ediatric,”“polymorphism,”“MTHFR,”“C677T,”“folate,”and “mutation.”An upper date limit of August 30,2009was applied;we used no lower date limit.The search was conducted without any restrictions on language but focused on stud-ies that had been conducted on human subjects.We also reviewed the Cochrane Library for relevant articles.The reference lists of reviews and retrieved articles were hand-searched simultaneously.Only published studies with full text articles were included.When more than one instance of the same patient population was included in several publications,only the most recent or complete study was used in this meta-analysis.2.2.Data extraction

The following information was extracted from each study:first author,year of publication,ethnicity of study population,genotyping method,and the num-ber of cases and controls for the C677T genotype.We did not define any

0145-2126/$–see front matter © 2010 Elsevier Ltd. All rights reserved.doi:10.1016/j.leukres.2010.03.034