Abstract
BackgroundPolymorphisms in genes involved in the metabolism of folate and methyl groups have been implicated with risk of digestive system cancer. Methionine synthase (MTR) plays a central role in folate metabolism, thereby affecting DNA methylation. The association between A2756G polymorphism (rs1805087) in MTR and digestive system cancer susceptibility was inconsistent in previous studies. To investigate this inconsistency, we performed this meta-analysis.MethodsDatabases including Pubmed, EMBASE, ISI Web of Science and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Potential sources of heterogeneity were also assessed by subgroup analysis and meta-regression.ResultsA total of 29 articles with 15,368 patients and 23,959 controls were included. We found no association between MTR A2756G polymorphism and digestive system cancer in overall population (G allele: OR = 1.03, 95% CI = 0.98–1.09, P = 0.25; dominant model: OR = 1.03, 95% CI = 0.97–1.10, P = 0.33; recessive model: OR = 1.02, 95% CI = 0.89–1.17, P = 0.79). In the stratified analyses according to cancer type, sample size and genotyping method, no evidence of any gene-disease association was obtained in almost all genetic models. However, marginal significant associations were found for East Asians and hospital-based studies.ConclusionsThis meta-analysis suggests that there is no significant association between the MTR A2756G polymorphism and digestive system cancer risk.
Highlights
It is predicted that by 2020, the number of new cases of cancer in the world will increase to more than 15 million, with deaths increasing to 12 million [1]
Genetic association studies published before the end of Sep. 2012 on digestive system cancer and polymorphism within MTR gene were identified through a search of PubMed, EMBASE, ISI Web of Science, and China National Knowledge Infrastructure (CNKI) (Chinese National Knowledge Infrastructure) without language restrictions using the following keywords and subject terms: ‘methionine synthase’ or ‘MTR’, ‘polymorphism’ or ‘variation’, and ‘cancer’ or ‘carcinoma’ or ‘neoplasm’
Studies included in the meta-analysis had to meet all the following criteria: (1) original papers containing independent data, (2) case–control or cohort studies, (3) association between MTR polymorphism and digestive system cancer risk was explored (4) identification of digestive system cancer cases was confirmed histologically or pathologically and (5) genotype distribution information or odds ratio (OR) with its 95% confidence interval (CI) and P-value
Summary
It is predicted that by 2020, the number of new cases of cancer in the world will increase to more than 15 million, with deaths increasing to 12 million [1]. In European countries, there were an estimated 0.91 million new cases of digestive system cancers (436,000 CRC and 149,000 GC) and 0.59 million deaths from these health care problems in 2008 [3]. Methionine synthase, a vitamin B 12 dependent enzyme, plays an important role in folate metabolism [10]. Polymorphisms in genes involved in the metabolism of folate and methyl groups have been implicated with risk of digestive system cancer. Methionine synthase (MTR) plays a central role in folate metabolism, thereby affecting DNA methylation. The association between A2756G polymorphism (rs1805087) in MTR and digestive system cancer susceptibility was inconsistent in previous studies. To investigate this inconsistency, we performed this meta-analysis
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