5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Acute Lymphoblastic Leukemia Risk: A Meta-analysis
- 1 October 2006
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Epidemiology, Biomarkers & Prevention
- Vol. 15 (10), 1956-1963
- https://doi.org/10.1158/1055-9965.epi-06-0334
Abstract
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)Keywords
This publication has 34 references indexed in Scilit:
- Is there a folate‐related gene‐environment interaction in the etiology of childhood acute lymphoblastic leukemia?International Journal of Cancer, 2006
- Adult Acute Lymphoblastic LeukemiaMayo Clinic Proceedings, 2005
- MTHFR genetic polymorphisms and susceptibility to childhood acute lymphoblastic leukemiaBlood, 2005
- The MTHFR C677T and A1298C Polymorphisms and Susceptibility to Childhood Acute Lymphoblastic Leukemia in PortugalJournal of Pediatric Hematology/Oncology, 2005
- Relationship between polymorphisms in genes involved in homocysteine metabolism and maternal risk for Down syndrome in BrazilAmerican Journal of Medical Genetics Part A, 2005
- Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemiaAmerican Journal of Hematology, 2003
- Does the Interaction between Maternal Folate Intake and the Methylenetetrahydrofolate Reductase Polymorphisms Affect the Risk of Cleft Lip with or without Cleft Palate?American Journal of Epidemiology, 2003
- Methylenetetrahydrofolate reductase (MTHFR): incidence of mutations C677T and A1298C in Brazilian population and its correlation with plasma homocysteine levels in spina bifidaAmerican Journal of Medical Genetics Part A, 2002
- A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductaseNature Genetics, 1995
- Meta-analysis in clinical trialsControlled Clinical Trials, 1986