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.
Highlights
Characterized as an uncontrolled growth of cells, cancer is a multi-stage and multi-factorial process (Mendis, 2014) with environmental factors, such as diet, lifestyle habits (Tomasetti and Vogelstein, 2015), and a genetic predisposition, conferring a strong individual risk
Low levels of folate or defects in folate metabolism may increase the risk of DNA strand breaks, aberrant DNA methylation, or even deficiencies in the DNA repair process, all of which are associated with an increased risk of cancer development (Suzuki and Bird, 2008)
Two hundred and sixty-six publications were excluded because they were conference abstracts or reviews, focused on animals or cell lines, did not focus on the Latino population, were about non-hematologic cancers, or did not examine the Methylenetetrahydrofolate reductase (MTHFR) polymorphisms
Summary
Characterized as an uncontrolled growth of cells, cancer is a multi-stage and multi-factorial process (Mendis, 2014) with environmental factors, such as diet, lifestyle habits (Tomasetti and Vogelstein, 2015), and a genetic predisposition, conferring a strong individual risk. Methylenetetrahydrofolate reductase (MTHFR) has been recently reported to be associated with diet and cancer development (Xie et al, 2014). With low folic acid consumption among Latin Americans (Brito et al, 2015), MTHFR, a key metabolite of the folate metabolism pathway, presents as a specific node between diet and cancer development. The mthfr gene is located on chromosome 1 and is a key enzyme for reducing 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (Crider et al, 2012). Low levels of folate or defects in folate metabolism may increase the risk of DNA strand breaks, aberrant DNA methylation, or even deficiencies in the DNA repair process, all of which are associated with an increased risk of cancer development (Suzuki and Bird, 2008). The C677T polymorphism is associated with a 66% and 25% decrease of enzymatic activity for the heterozygous and homozygous genotypes, respectively, whereas the A1298C polymorphism is associated with a less severe decrease of enzyme activity (Tang et al, 2014)
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