Association Between Cytokine Gene Polymorphisms and Gastric Precancerous Lesions: Systematic Review and Meta-analysis

Abstract

Polymorphisms within interleukin-1 (IL1) and tumor necrosis factor α (TNFA) gene clusters are associated with an increased risk of gastric cancer. However, their role in gastric precancerous lesions remains poorly understood. Our objective was to perform a meta-analysis of studies addressing the association between IL1B-511, IL1RN variable number of tandem repeat, and TNFA-308 gene polymorphisms and gastric precancerous lesions, including original data from Portugal and Mozambique. Published studies on the association between these cytokine gene polymorphisms and gastric precancerous lesions were identified by systematic review, and estimates of the association were combined using random-effects meta-analysis taking into account new data obtained from Portuguese volunteer shipyard workers (n = 215) and Mozambican dyspeptic patients (n = 96) who underwent endoscopic and pathologic evaluation following the same protocol. Odds ratio (OR) estimates for intestinal metaplasia were 2.83 [95% confidence interval (95% CI), 1.15-6.96] for the IL1RN*22 genotype, 1.86 (95% CI, 1.03-3.36) for IL1B-511 T carriers, and 0.59 (95% CI, 0.12-3.04) for the TNFA-308*AA genotype in the Portuguese sample. All Mozambican subjects with intestinal metaplasia were T carriers for IL1B-511 and none had the 2 allele for IL1RN. In meta-analysis, IL1RN*22 genotype was associated with an increased risk of gastric precancerous lesions (22 The IL1RN*22 genotype seems to consistently increase the risk of gastric precancerous lesions, supporting a role for this polymorphism in the early stages of gastric carcinogenesis.

Association of Cytokine Gene Polymorphisms with Gastritis in a Kazakh Population

“…In the populations of East Asia and Europe alleles of interleukin-1 beta are associated with an increased risk of atrophic gastritis and gastric cancer (El-Omar et al, 2000;Matsukura et al, 2003;Yamada et al, 2006). A meta-analysis study on the relationship of IL1B polymorphism with the development of precancerous conditions of the stomach was conducted by Peleteiro et al (Peleteiro et al, 2010). In particular, there is a weak association of the development of gastric epithelial metaplasia in carriers of T allele at position IL1B-511 (OR=1.86) (Peleteiro et al, 2010).…”

“…A meta-analysis study on the relationship of IL1B polymorphism with the development of precancerous conditions of the stomach was conducted by Peleteiro et al (Peleteiro et al, 2010). In particular, there is a weak association of the development of gastric epithelial metaplasia in carriers of T allele at position IL1B-511 (OR=1.86) (Peleteiro et al, 2010). Previously, the association of IL1B-511T/-31C alleles and IL1RN*2 with the risk of gastric cancer has been shown in the European population by El-Omar et al (El-Omar et al, 2000).…”

A Polymorphism of the MMP-1, EGF, and IL-LB Gene Is Not Correlated with Gastric Carcinogenesis

“…Recent meta-analysis showed that only the IL1RN×22 Genotype seems to consistently increase the risk of gastric precancerous lesions, supporting a role for this polymorphism in the early stages of gastric carcinogenesis. 25 Therefore, it seems that the presence of C/T genotypes in the IL-1B-31 did not increase the susceptibility for the development of gastric carcinoma, especially in early stages. This discrepancy between our results and previous results will be due to small sample number and ethnic differences.…”

Molecular Mechanism of Gastric Carcinogenesis in Helicobacter pylori-Infected Rodent Models

“…pylori infection-mediated cytokine expression is essentially involved in the development of chronic gastritis and stomach tumors. TNF-α and IL-1β are considered to be particularly important, because epidemiological studies have suggested that their polymorphisms are associated with the increased risk of gastric carcinogenesis [103][104][105]. Oshima et al recently reported that additional knockout of TNF-α or TNF-α receptor results in the significant suppression of gastric tumor development in the K19-Wnt1/C2mE mice [106].…”