title: Variants of the MTHFR gene and susceptibility to acute lymphoblastic leukemia in children: a synthesis of genetic association studies.
abstract: BACKGROUND
  Acute lymphoblastic leukemia (ALL) is a complex disease with genetic background. The genetic association studies (GAS) that investigated the association between ALL and the MTHFR C677T and A1298C gene variants have produced contradictory or inconclusive results.
  
  
  METHODS
  In order to decrease the uncertainty of estimated genetic risk effects, a meticulous meta-analysis of published GAS related the variants in the MTFHR gene with susceptibility to ALL was conducted. The risk effects were estimated based on the odds ratio (OR) of the allele contrast and the generalized odds ratio (OR(G)). Cumulative and recursive cumulative meta-analyses were also performed.
  
  
  RESULTS
  The analysis showed marginal significant association for the C677T variant, overall [OR=0.91 (0.82-1.00) and OR(G)=0.89 (0.79-1.01)], and in Whites [OR=0.88 (0.77-0.99) and OR(G)=0.85 (0.73-0.99)]. The A1298C variant produced non-significant results. For both variants, the cumulative meta-analysis did not show a trend of association as evidence accumulates and the recursive cumulative meta-analysis indicated lack of sufficient evidence for denying or claiming an association.
  
  
  CONCLUSIONS
  The current evidence is not sufficient to draw definite conclusions regarding the association of MTHFR variants and development of ALL.
authors.affiliation: Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece. zintza@med.uth.gr
authors.forename: Elias
authors.initials: E
authors.lastname: Zintzaras
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Doxani
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Rodopoulou
authors.forename: Georgios
authors.initials: G
authors.lastname: Bakalos
authors.forename: Dimitris C
authors.initials: DC
authors.lastname: Ziogas
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Ziakas
authors.forename: Michael
authors.initials: M
authors.lastname: Voulgarelis
mesh_terms: D002648:Child; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)