Methylenetetrahydrofolate reductase gene polymorphism and risk of chronic myelogenous leukemia: a meta-analysis.

PURPOSE: Reported evidence supports a role for methylenetetrahydrofolate reductase (MTHFR) in the risk of chronic myelogenous leykemia (CML). However, these reports arrived at non-conclusive and even conflicting results regarding the association between two common MTHFR polymorphisms (C677T and A1298C) and CML risk. Thus, a meta-analysis was carried out to clarify a more precise association between these two polymorphisms and the CML risk by updating the available publications. METHODS: Pooled odds ratios (OR) with corresponding 95% confidence interval (95% CI) and stratification analysis were performed to estimate the relationship between MTHFR polymorphisms and the risk of CML under different genetic comparison models. RESULTS: Data from the meta-analysis showed no significant association between MTHFR C677T polymorphism and CML risk. However, significant associations were found between MTHFR A1298C variants and CML risk under homozygous comparison model (CC vs AA, OR=1.62, 95% CI=1.11-2.36, p=0.01) and dominant comparison model (CC+AC vs AA, OR=1.68, 95% CI=1.17-2.43, p=0.005) in overall population; especially more obvious impacts were noticed for Asian populations in subgroup analysis for homozygous model (CC vs AA, OR=2.00, 95% CI=1.25-3.21, p=0.004) and dominant model (CC+AC vs AA, OR=2.49, 95% CI=1.42-4.36, p=0.001), but this did not apply in Caucasian populations. CONCLUSION: The results of this meta-analysis suggested no significant association between MTHFR C677T polymorphism and CML risk, while an increased CML risk was noticed for 1298C variant carriers, especially in Asian populations but not in Caucasian populations, which suggested ethnicity differences between MTHFR A1298C polymorphisms and risk of CML.