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 been associated with acute lymphoblastic leukemia (ALL). However, results were conflicting. The aim of this study was 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 studies containing 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 10,850 controls were identified. The meta-analysis stratified by ethnicity showed that individuals with the homozygous TT genotype had decreased risk of ALL (OR=0.776, 95% CI: 0.687 similar to 0.877, p<0.001) in Caucasians (OR= 0.715, 95% CI: 0.655 similar to 0.781, p= 0.000). However, results among Asians (OR=0.711, 95% CI: 0.591 similar to 1.005, p= 0.055) and others (OR=0.913, 95% CI: 0.656 similar to 1.271, p= 0.590) did not suggest an association. A symmetric funnel plot, 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 ALL in Caucasians. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between the MTHFRC677T polymorphism and ALL.