Lack of Association between Methionine Synthase A2756G Polymorphism and Digestive System Cancer Risk: Evidence from 39327 Subjects

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.

Associations of MTHFR Gene Polymorphisms with Hypertension and Hypertension in Pregnancy: A Meta-Analysis from 114 Studies with 15411 Cases and 21970 Controls

“…In addition, hospital based and small sample size studies seem to have stronger associations than population based and large sample size studies. Hospital based studies are prone to produce unreliable results because controls from hospital based studies are less representative of the general population, especially when the polymorphism under investigation are expected to be related to disorders that the hospital based controls may have [142] , [143] . Small sample with limited participants is often accompanied with selection biases, and lacks sufficient power to support or deny an association [144] .…”

Association study between genetic polymorphisms in folate metabolism and gastric cancer susceptibility in Chinese Han population: A case–control study

“…Evidences have been provided that G allele of MTR A2756G polymorphism was associated with multiple diseases, such as autism, head, and neck cancer (Galbiatti et al, 2010;Haghiri, Mashayekhi, Bidabadi, & Salehi, 2016). The GG genotype was reported to affect the DNA hypomethylation and individuals who carried 2756GG showed a lower frequency of CpG island hypermethylation in tumor suppressor genes (Goode, Potter, Bigler, & Ulrich, 2004;Zhao et al, 2013).…”

Gene-Gene Interaction Study Between Genetic Polymorphisms of Folate Metabolism and MTR SNPs on Prognostic Features Impact for Breast Cancer

“…On the other side, other studies reported no significant association with susceptibility to breast cancer (24), while others demonstrated that it may be a reduced risk factor for lymphoblastic leukemia (ALL), colorectal cancer and gastric cancer (25,26). This conflict in data between the different studies may be attributed to geographic, ethnic variations and several factors such as a measurement sample, hormones, environmental factors, differences in dietary and intake of nutrients (26,27).…”