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5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Acute Lymphoblastic Leukemia Risk: A Meta-analysis

¹ Department of Biochemistry and Molecular Biology, Federal University of São Paulo; ² Clinical and Toxicological Analysis Department, Faculty of Pharmaceutical Sciences, and ³ Heart Institute (Instituto do Coração), São Paulo University Medical School, University of São Paulo; ⁴ Division of Experimental Medicine, Instituto Nacional de Câncer, Rio de Janeiro, Rio de Janeiro, Brazil; and ⁵ Fleury Research Institute, São Paulo, São Paulo, Brazil

Requests for reprints: Tiago V. Pereira, Department of Biochemistry and Molecular Biology, Federal University of São Paulo, Instituto do Coração, Avenida Dr. Enéas de Carvalho Aguiar 44, CEP 05403-000, São Paulo, SP, Brazil. Phone: 55-11-3069-5068; Fax: 55-11-3069-5068. E-mail: t27026t{at}yahoo.com.br

There is evidence supporting a role for 5-10 methylenetetrahydrofolate reductase (MTHFR) gene variants in acute lymphoblastic leukemia (ALL). To provide a more robust estimate of the effect of MTHFR polymorphisms on the risk of ALL, we did a meta-analysis to reevaluate the association between the two most commonly studied MTHFR polymorphisms (C677T and A1298C) and ALL risk. All case-control studies investigating an association between the C677T or A1298C polymorphisms and risk of ALL were included. We applied both fixed-effects and random-effects models to combine odds ratio (OR) and 95% confidence intervals (95% CI). Q-statistic was used to evaluate the homogeneity and both Egger and Begg-Mazumdar tests were used to assess publication bias. The meta-analysis of the C677T polymorphism and risk of childhood ALL included 13 studies with a total of 4,894 individuals. Under a fixed-effects model, the TT genotype failed to be associated with a statistically significant reduction of childhood ALL risk (TT versus CT + CC: OR, 0.88; 95% CI, 0.73-1.06; P = 0.18). However, individuals homozygous for the 677T allele exhibited a 2.2-fold decrease in risk of adult ALL (TT versus CT + CC: OR, 0.45; 95% CI, 0.26-0.77; P = 0.004). In both cases, no evidence of heterogeneity was observed. No association between the A1298C variant and susceptibility to both adult and childhood ALL was disclosed. Our findings support the proposal that the common genetic C677T polymorphism in the MTHFR contributes to the risk of adult ALL, but not to the childhood ALL susceptibility. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1956–63)

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