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.
ABSTRACT
BACKGROUND: Previous meta-analyses have shown an ethnic dependency of the C677T and the A1298C methylenetetrahydrofolate reductase (MTHFR) polymorphisms, with no focus on the Latino population. For Latinos, many studies have examined these polymorphisms and breast cancer susceptibility, yielding no concise result. Therefore, we undertook this meta-analysis to determine the effect these polymorphisms have on breast cancer risk for Latinos. METHODS: PubMed, EBSCO, LILACS, Scopus, and Latin American-specific databases were searched for studies exploring the association between the MTHFR polymorphisms and breast cancer susceptibility in Latinos until January 2019. Genotype distributions were extracted and, depending on the level heterogeneity determined by the ψ2-based Q test and the I2 test, fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) 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. RESULTS: Of the 280 retrieved publications, 9 studies were included: 9 for the C677T polymorphism and 5 for the A1298C polymorphism. For the C677T polymorphism, there was an elevated risk for the homozygous (OR 1.42, 95% CI 1.05-1.92), the dominant (OR 1.16, 95% CI 1.02-1.31), the recessive (OR 1.33, 95% CI 1.01-1.75), and the allelic model (OR 1.17, 95% CI 1.03-1.33, p < 0.01). No association between the A1298C polymorphism and the risk to develop breast cancer was determined. CONCLUSION: The results indicated that, for Latinos, the C677T polymorphism is associated with a significant risk for developing breast cancer, whereas the A1289C polymorphism does not.
