Assessment of the relationship between methylenetetrahydrofolate reductase polymorphism and acute lymphoblastic leukemia: Evidence from an updated meta-analysis

Abstract

Objective The methylenetetrahydrofolate reductase gene C677T polymorphism is closely related to the acute lymphoblastic leukemia. Several case–control studies have investigated this association; however, no conclusions could be drawn. A comprehensive updated meta-analysis is established to explain these contradictions and clarify the overall impact of this variant on the susceptibility to acute lymphoblastic leukemia. Methods Electronic searches were conducted to select published studies prior to June 2018. Pooled odds ratios and stratification analysis were performed under different genetic comparison models, age, and ethnicity. Results Totally, 66 case–control studies including 9619 acute lymphoblastic leukemia cases and 17,396 controls were selected. Our analyses showed that methylenetetrahydrofolate reductase C677T polymorphism was protective mainly in Asian and European countries, under all genetic models and regardless of age, but leukemogenic in mixed population. Conclusion Thus, C677T polymorphism may be a promising acute lymphoblastic leukemia biomarker, but they should be interpreted with caution considering other factors such as folic acid intake, gene–gene and gene–environment interactions.

MTHFR 677T-1298C haplotype in acute lymphoblastic leukemia: Impact on methotrexate therapy

“…As mentioned above, there is evidence supporting a role for MTHFR gene variants in ALL. 4,[21][22][23] Moreover, the carriers of the variant alleles of both the MTHFR polymorphisms analyzed have decreased enzyme activity. 3,24 Therefore, it seems reasonable to analyze both variants and genotype combinations.…”

Involvement of MTHFR rs1801133 in the Susceptibility of Acute Lymphoblastic Leukemia: A Preliminary Study

“…[8][9][10][11][12][13][14][15][16][17] In addition, an updated meta-analysis noticed a significantly reduced risk of ALL with MTHFR C677T polymorphism. 25 The discrepancy in the results related to the association between the 5,10-MTHFR 677COT polymorphism and ALL risk might be because of the heterogeneity in methodology and sample size, and other factors (geneenvironment interactions and folate status). 26 In addition to the significant association between MTHFR rs1801133 and ALL, a high frequency of this variant was observed particularly in childhood ALL, B-phenotype, and a higher risk-related treatment group in Tunisian patients.…”

“…However, most of the studies highlight a decreased risk 8–17. In addition, an updated meta-analysis noticed a significantly reduced risk of ALL with MTHFR C677T polymorphism 25. The discrepancy in the results related to the association between the 5,10- MTHFR 677COT polymorphism and ALL risk might be because of the heterogeneity in methodology and sample size, and other factors (gene-environment interactions and folate status) 26…”

Pharmacogenomics of Leukemia; Unlocking Personalized Treatment Strategies

“…It plays a significant role in leukemia treatment, genetic variations among patients can impact drug metabolism, drug efficacy, treatment response, and the risk of adverse effects (Frikha 2020). Provided below are some key ways in which genetic polymorphism is relevant in leukemia treatment: Genetic variations in CYP3A4 and CYP3A5 enzymes can influence the metabolism of drugs like imatinib, dasatinib, and vincristine, commonly used in leukemia treatment (Yang et al 2014).…”