Tumour-necrosis factor-A polymorphisms and gastric cancer risk: a meta-analysis

Abstract

Inflammation is one of the early phases in the development of gastric cancer. Therefore, several studies have examined the association of polymorphisms in tumour-necrosis factor-A gene (TNF-A) with gastric cancer risk. This meta-analysis reviews and summarises published evidence for these associations. Searching several databases yielded 24 independent studies that reported on the associations between TNF-A polymorphisms and gastric cancer risk. We analysed available data for the most commonly investigated polymorphisms: TNF-A -308G4A (23 studies), TNF-A -238G4A (9 studies), and TNF-A -857C4T (5 studies). Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated in the random-effects model using the DerSimonian -Laird method. Q-statistic and I 2 -statistic were calculated to examine heterogeneity, and funnel plots were plotted to examine small study effects. The overall ORs (95% CIs) for AG and AA genotypes vs GG genotype for TNF-A -308 were 1.09 (0.94 -1.27) and 1.49 (1.11 -1.99), respectively. For TNF-A -238, the corresponding ORs (95% CIs) were 1.05 (0.84 -1.33) and 1.25 (0.30 -5.26), respectively. The overall ORs (95% CIs) for CT and TT genotypes (vs CC) for TNF-A -857 were 1.06 (0.89 -1.27) and 1.57 (0.91 -2.70), respectively. The statistically significant association between TNF-A -308GG and gastric cancer was limited to western populations. This association showed little heterogeneity (I 2 ¼ 0) and remained consistently strong when analyses were limited to anatomic and histologic subtypes of gastric cancer, or limited to studies in which genotype frequencies were in Hardy -Weinberg equilibrium, or limited to larger studies. These same subgroup analyses did not change results associated with other polymorphisms. In conclusion, TNF-A -308AA genotype was associated with a statistically significant increased risk of gastric cancer, whereas other studied polymorphisms were not. The association between TNF-A -857TT genotype and gastric cancer was near significant, and may become significant if more studies are published.

Pickled vegetables and the risk of oesophageal cancer: a meta-analysis

“…As in our previous meta-analyses (Gorouhi et al, 2008;Islami and Kamangar, 2008), we present the results for larger studies, defined as those with s.e. p0.5 separately.…”

MicroRNA dysregulation in gastric cancer: a new player enters the game

“…Polymorphisms of various genes, such as CDH1 (Humar et al, 2002), GSTT1 (Saadat, 2006), IL1RN (Rocha et al, 2005), MTHFR , TP53 (Zhou et al, 2007) and TNF-A (Gorouhi et al, 2008), have been shown to be associated with gastric cancer. Aside from these candidate genes, some recent studies suggest that polymorphisms in the miRNA genes may serve as novel risk predictors for gastric cancer.…”

Tumor Necrosis Factor Alpha Extended Haplotypes and Risk of Gastric Carcinoma

“…The TNFA-308G>A promoter SNP is one of the most frequently reported candidate host factors associated with the risk for gastric carcinoma. However, the increasing number of published studies has revealed a conspicuous lack of reproducibility among the various populations (23,24). So far, it is not known whether the TNFA-308G>A SNP is acting as an etiologic susceptibility locus or if it is associated in linkage disequilibrium with a causal sequence variant that has not yet been identified.…”

“…Although several promoter polymorphisms have been analyzed, most studies have focused on the TNFA-308G>A (rs1800629). Since the first reports of TNFA association with gastric carcinoma (18)(19)(20)(21)(22), the TNFA-308*A allele has emerged as an important candidate accounting for the increased risk of gastric carcinoma development (23,24). Nevertheless, outcomes of the numerous studies on whether polymorphisms in or near TNF genes do underlie these associations are conflicting.…”

“…Relatively to this SNP, we have confirmed the established association (22) between individuals carrying the TNFA-308*A allele and increased risk for developing gastric carcinoma (OR, 1.7; 95% CI, 1.3-2.2). In fact, two recent meta-analyses (23,24) identify the -308G>A as the single TNFA SNP displaying Kamangar et al 2006 (35). The present understanding of the role of the TNFA-308G>A polymorphism on susceptibility to disease only emphasizes the importance of extending single-SNP association studies to haplotype-based approaches.…”