The MTHFR C677T Polymorphism and Risk of Acute Lymphoblastic Leukemia: an Updated Meta-analysis Based on 37 Case-control Studies

Background: The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) has beenassociated with acute lymphoblastic leukemia (ALL). However, results were conflicting. The aim of this studywas to quantitatively summarize the evidence for the MTHFRC677T polymorphism and ALL risk.
Methods:Electronic searches of PubMed and the Chinese Biomedicine database were conducted to select case-control studiescontaining available genotype frequencies of C677T and the odds ratio (OR) with 95% confidence interval (CI)was used to assess the strength of any association.
Results: Case-control studies including 6,371 cases and 10,850controls were identified. The meta-analysis stratified by ethnicity showed that individuals with the homozygousTT genotype had decreased risk of ALL (OR= 0.776, 95% CI: 0.687~0.877, p< 0.001) in Caucasians (OR= 0.715,95% CI: 0.655~0.781, p= 0.000). However, results among Asians (OR=0.711, 95% CI: 0.591~1.005, p= 0.055)and others (OR=0.913, 95% CI: 0.656~1.271, p= 0. 590) did not suggest an association. A symmetric funnelplot, the Egger’s test (P=0.093), and the Begg- test (P=0.072) were all suggestive of the lack of publication bias.
Conclusion: This meta-analysis supports the idea that the MTHFR C677T genotype is associated with risk of ALLin Caucasians. To draw comprehensive and true conclusions, further prospective studies with larger numbersof participants worldwide are needed to examine associations between the MTHFRC677T polymorphism andALL.