Lack of Impact of the A1298C MTHFR on the Risk of Childhood Acute Lymphoblastic Leukemia: Evidence from a Meta-analysis

To clarify the effect of the A1298C variant of methylenetetrahydrofolate reductase (MTHFR) gene on the risk of acute lymphoblastic leukemia (ALL), an updated meta-analysis was performed. Electronic literature search was carried out in PubMed to collect relevant articles. Pooled odds ratios (OR) and stratification analysis were achieved under different genetic comparison models, age and ethnicity. A total of 46 articles including 7020 cases and 12,114 controls were enrolled. Overall, no significant association was observed for the MTHFR A1298C variant on the risk of ALL in any genetic model test, when all the studies pooled together (OR ~ 1 0.91; p > 0.05). In subgroup analyses stratified by age and ethnicity, the MTHFR A1298C reduce the risk of ALL in adult under allele contrast (OR = 0.88; [0.72; 1.09], p = 0.23) mainly in Caucasian populations. The present meta-analysis provides evidence that the A1298C variant of MTHFR gene is unlikely to be a major risk gene for childhood ALL.