Abstract
Plenty of studies have investigated the effect of methionine synthase (MTR) A2756G polymorphism on risk of developing pediatric acute lymphoblastic leukemia (ALL), but the available results were inconsistent. Therefore, a meta-analysis was conducted to derive a more precise estimation of the association between MTR A2756G polymorphism and genetic susceptibility to pediatric ALL. The PubMed, Embase, Google Scholar, Web of Science, ScienceDirect, Wanfang Databases and China National Knowledge Infrastructure were systematically searched to identify all the previous published studies exploring the relationship between MTR A2756G polymorphism and pediatric ALL risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the strength of association. Sensitivity analysis and publication bias were also systematically assessed. This meta-analysis finally included ten available studies with 3224 ALL cases and 4077 matched controls. The results showed that there was significant association between MTR A2756G polymorphism and risk of pediatric ALL in overall population (AG vs. AA: OR = 1.13, 95%CI = 1.02–1.26, P = 0.02; AG+GG vs. AA: OR = 1.13, 95%CI = 1.02–1.25, P = 0.01; G allele vs. A allele: OR = 1.10, 95%CI = 1.01–1.20, P = 0.03). In the stratification analyses by ethnicity, quality score and control source, significant association was found in Caucasians, population-based designed studies and studies assigned as high quality. In conclusion, this meta-analysis suggests that MTR A2756G polymorphism may influence the development risk of pediatric ALL in Caucasians. Future large scale and well-designed studies are required to validate our findings.
Highlights
Received: 04 October 2018Revised: 02 December 2018Accepted: 06 December 2018Accepted Manuscript Online: Version of Record published: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, which accounts for 30%of all malignancy diagnosed in children and 80% of pediatric leukemia [1]
Epidemiological studies suggest that the imbalance of folate metabolism may be involved in predisposition to carcinogenesis, which is based on its involvement in both DNA biosynthesis and DNA methylation [5]
When all eligible studies were pooled together, the results found that there was statistically significant association between methionine synthase (MTR) A2756G polymorphism and risk of pediatric
Summary
Received: 04 October 2018Revised: 02 December 2018Accepted: 06 December 2018Accepted Manuscript Online: Version of Record published: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, which accounts for 30%of all malignancy diagnosed in children and 80% of pediatric leukemia [1]. Accepted Manuscript Online: Version of Record published: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, which accounts for 30%. As for many cancers, the interactions between susceptibility genes and environmental factors are likely to implicate in the development of ALL. Epidemiological studies suggest that the imbalance of folate metabolism may be involved in predisposition to carcinogenesis, which is based on its involvement in both DNA biosynthesis and DNA methylation [5]. Gene-specific hypermethylation and global DNA hypomethylation are two of the most frequently observed altered DNA methylation patterns in tumors [8,9]. Accumulating studies have reported that polymorphisms in genes encoding folate-metabolizing enzymes disturb the balance of folate metabolism and have been associated with an altered predisposition to cancer [10,11,12]
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