Differential effects of the methylenetetrahydrofolate reductase polymorphisms (C677T and A1298C) on hematological malignancies among Latinos: a meta-analysis

Abstract

Our objective was to determine the association between the methylenetetrahydrofolate reductase polymorphisms (C677T and A1298C) and the risk of developing acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), acute myeloid leukemia (AML), and multiple myelomas (MM) in Latinos. PubMed, SCOPUS, EBSCO, LILACS, and other Latin-specific databases were searched for case-control studies that investigated the association between these polymorphisms and hematologic malignancies until November 2017. Genotype distributions were extracted and either fixed-effects or random-effects models were used to calculate the pooled crude odds ratios (ORs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. No publication bias was detected by the Begg-Mazumdar’s test and Egger’s test. From 290 publications, we identified 15 studies on the C677T polymorphism and 13 studies on the A1298C polymorphism. We observed a significant decrease in risk for the C677T polymorphism (OR range=0.54-0.75, p<0.01) and a significant increase in risk for the A1298C polymorphism (OR range=1.28-2.52, p<0.05) in developing ALL for all genetic models. No associations were determined for CML, AML, or MM for either polymorphism. This meta-analysis demonstrated that the A1298C polymorphism was associated with an increased risk of developing ALL, whereas the C677T polymorphism was associated with a decreased risk (protective factor) in the Latino population.

Association between A1298C and C677T methylenetetrahydrofolate reductase gene polymorphisms and the risk of acute lymphoid and myeloid leukemia

“…A large number of studies have examined the association between polymorphisms of MTHFR gene and some cancers, diseases, and birth defect such as nonfamilial colorectal cancer, hepatocellular carcinoma, diabetic nephropathy, distal corectal adenoma, Down syndrome and spontaneous abortion [9][10][11]. There is some evidence that confirms the role of polymorphism in MTHFR-related genes in patients with ALL (acute lymphoblastic leukemia) and AML (acute myeloid leukemia) [1,12,13]. MTHFR is a key enzyme in the regulation of folic acid pathway and converts 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate.…”

“…Several polymorphisms of MTHFR enzyme have been identified from which the C677T and A1298C are the most important ones. C677T occurs in exon 4 and results in an alanine to valin change at codon 222 while the second common polymorphism A1298C, is transversion of A to C at position 1298, results in glutamate to alanine in codon 7 [15,16]. These polymorphisms decrease the enzyme activity and change distribution of intracellular folate metabolites that cause accumulation of 5-10 MTHFR, the precursor for synthesis of purine and thymidylate [16,17].…”