The relationship between tumor necrosis factor-α polymorphisms and gastric cancer risk: An updated meta-analysis

Abstract

The aim of the present study was to evaluate the relationship between tumor necrosis factor-α (TNF-α) and the development of gastric cancer, and to investigate whether it can be used as a biological marker for gastric cancer. In the current study, a new meta-analysis was performed to assess the association between TNF-α gene polymorphisms and gastric cancer susceptibility. Subgroup analyses based on ethnicity, control population source and non-cardia cancers were also conducted. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. TNF-α 308 polymorphisms indicated a significant relationship with gastric cancer risk among a normal population [GA/AA vs. GG; 1.17 (1.10–1.23)]. In analysis stratified by ethnicity, TNF-α 238 displayed an association with gastric cancer risk in eastern populations [GA/AA vs. GG: 1.24 (1.02–1.50)], but not in western populations [GA/AA vs. GG: 0.96 (0.79–1.18)]. The overall ORs (95% CIs) for TNF-α 857, TNF-α 1031 and TNF-α 863 were 1.13 (1.04–1.24), 0.94 (0.85–1.05) and 0.89 (0.78–1.02), respectively, under dominant genetic model comparison. Among the above three SNPs, only TNF-α 857 was robustly associated with gastric cancer inclination, and this association remained consistently robust when limited to non-cardia gastric cancers [GA/AA vs. GG: 1.16 (1.03–1.31)]. TNF-α 308 and TNF-α 857 genotypes were potential risk factors of statistical significance in gastric cancer, and TNF-α 238 indicated to be significantly associated with gastric cancer risk only in eastern populations. TNF-α 1031 and TNF-α 863 were not significantly associated with gastric cancer risk.

Risk factors associated with gastric malignancy during chronic Helicobacter pylori infection

“…TNF-α plays an important role in maintaining homeostasis of the immune system and host defense, and is overexpressed in the gastric mucosa of Hpinfected patients 75,76 . In particular, TNF-α-307A (historically mislabeled as position 308) is described to increase its expression 77 and is associated with increased risk of developing gastric cancer [78][79][80] . While additional polymorphisms have been detected at TNF-α-238 (only in Eastern populations), -857, -863, and -1031, not all identified single nucleotide polymorphisms (SNP) have been associated with gastric malignancy 80 .…”

“…In particular, TNF-α-307A (historically mislabeled as position 308) is described to increase its expression 77 and is associated with increased risk of developing gastric cancer [78][79][80] . While additional polymorphisms have been detected at TNF-α-238 (only in Eastern populations), -857, -863, and -1031, not all identified single nucleotide polymorphisms (SNP) have been associated with gastric malignancy 80 . Notably, there is not complete consensus as to the biological relevance of the TNF-α-307A SNP, as another study reported that mucosal expression of TNF-α or inflammation, in response to Hp infection between populations harboring the parental sequence and populations harboring the TNF-α-307A SNP, were not statistically different 73 .…”

Tumour necrosis factor-α(-308) polymorphism and the risk of gastric cancer: A meta- analysis and trial sequential analysis

“…The vast majority of included studies had evidence of HWE. Numerous studies had highlighted the issue of deviations from HWE in genetic association studies such as genotyping error, population admixture/substructure, among others [58][59][60]. Furthermore, for robustness of the findings, we have attempted several subgroup analyses.…”

“…Furthermore, for robustness of the findings, we have attempted several subgroup analyses. Additionally, there are some strengths in this meta-analysis compared with published reviews in this field [11,50,51,[58][59][60]. To be comprehensive, we have attempted the TSA technique, which is useful to adjust random-error risk.…”

Prevalence of <i>Helicobacter pylori cag</i>A and <i>sab</i>A Genotypes in Patients with Gastric Disease

“…Gastric cancer is one of the most common types of cancer worldwide and the third leading cause of cancer death. It is responsible for about 720,000 deaths per year around the world, and its occurrence is very frequently in Asian countries [1] [2]. The onset of cancer usually starts with lesions, which evolve into an in- flammation that tends to be followed by chronic gastritis, gastric atrophy, and finally gastric cancer [3].…”