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

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 -308G>A (23 studies), TNF-A -238G>A (9 studies), and TNF-A -857C>T (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)=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.