Abstract
Methionine synthase (MTR), which plays a central role in maintaining adequate intracellular folate, methionine and normal homocysteine concentrations, was thought to be involved in the development of colorectal cancer (CRC) and colorectal adenoma (CRA) by affecting DNA methylation. However, studies on the association between MTR A2756G polymorphism and CRC/CRA remain conflicting. We conducted a meta-analysis of 27 studies, including 13465 cases and 20430 controls for CRC, and 4844 cases and 11743 controls for CRA. Potential sources of heterogeneity and publication bias were also systematically explored. Overall, the summary odds ratio of G variant for CRC was 1.03 (95% CI: 0.96–1.09) and 1.05 (95% CI: 0.99–1.12) for CRA. No significant results were observed in heterozygous and homozygous when compared with wild genotype for these polymorphisms. In the stratified analyses according to ethnicity, source of controls, sample size, sex, and tumor site, no evidence of any gene-disease association was obtained. Results from the meta-analysis of four studies on MTR stratified according to smoking and alcohol drinking status showed an increased CRC risk in heavy smokers (OR = 2.06, 95% CI: 1.32–3.20) and heavy drinkers (OR = 2.00, 95% CI: 1.28–3.09) for G allele carriers. This meta-analysis suggests that the MTR A2756G polymorphism is not associated with CRC/CRA susceptibility and that gene-environment interaction may exist.
Highlights
Colorectal cancer (CRC) is the third most common malignancy and the fourth most frequent cause of cancer deaths worldwide
Search term combinations were keywords relating to the methionine synthase (e.g., ‘‘methionine synthase’’, ‘‘MTR’’, ‘‘one-carbon metabolism’’) in combination with words related to CRC/Colorectal adenoma (CRA) (e.g., ‘‘colorectal cancer’’, ‘‘colorectal tumor’’, ‘‘colorectal carcinoma’’, ‘‘rectal cancer’’, ‘‘colon cancer’’, and ‘‘colorectal adenoma’’) and ‘‘polymorphism’’ or ‘‘ variation’’
A total of 27 studies were retrieved based on the search criteria for CRC/CRA susceptibility related to the MTR A2756G polymorphism [20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46]
Summary
Colorectal cancer (CRC) is the third most common malignancy and the fourth most frequent cause of cancer deaths worldwide. More than one million new cases of CRC are diagnosed annually, and nearly 530,000 individuals die from CRC every year [1]. The etiology of CRC is complex and multifactorial. Hereditary syndromes, such as familial adenomatous polyposis and hereditary nonpolyposis CRC, account for ,10% of all cases [2]. The majority of cases are thought to be caused by multiple factors, which include dietary and lifestyle habits and/or mild genetic predisposition [3]. Colorectal adenoma (CRA) is a recognized precursor of CRC based on epidemiologic, histological, and genetic studies demonstrating shared genetic alterations [4,5]
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