Interleukin 1 gene polymorphism and gastric cancer risk with Helicobacter pylori: a meta-analysis

摘要

Helicobacter pylori infection is the single most common cause of gastric cancer. But the outcome of Helicobacter pylori infection is not only determined by bacterial virulence, environmental factors, but also host genetic factors. So inflammatory cytokine genetic polymorphisms can influence interindividual variation in gastric cancer susceptibility. IL-1 is an important proinflammatory cytokine, and four of IL-1 polymorphisms IL-1B-511C→T,IL-1B-31T→C,IL-1B+3954C→T,IL-1RN ~*2/~*2 have been extensively studied in the association with gastric cancer, although published studies have been inconclusive. To clarify the impact of IL-1 polymorphisms on gastric cancer risk, we performed a meta-analysis of the published data from eighteen individual case-control studies of 3760 gastric cancer cases and 3910 controls. The results showed that individuals with the IL-1B-31TT genotype had a 6%(odds ratio (OR)=1.37,95% confidence interval (CI)=1.09-1.73) increase risk of gastric cancer compared with individuals with the -31CC genotype. A stratified analysis with ethnicity showed that European IL-1B-31TT was associated with a statistically significant increase risk of gastric cancer (OR=1.83,95%CI=1.49 to 2.25), but Asian was not (OR=1.20,95%CI=0.89 to 1.60). Moreover, we stratified studies with H.pylori infection and found IL-1B-31TT was associated with a statistically significant increasing risk of gastric cancer in Hp positive (OR=1.95,95%CI=1.28 to 2.96) compared with IL-1B-31CC in Hp positive. But there was no evidence that IL-1B-511,+3954,IL-1RN were associated with increasing risk of gastric cancer whether Hp positive or negative. These results support the hypothesis that IL-1B-31 T is a risk allele and individuals with the IL-1B-31TT are higher risk of developing gastric cancer, especially in H.pylori infection and European.But these results did not support the hypothesis that IL-1B-511T,+3954T,IL-1RN~*2 are risk alleles and individuals with the IL-1B-511TT, IL-1B+3954TT and IL-1RN~*2/~*2 are at no higher risk of developing gastric cancer whether Hp infected or not. Large multi-center studies with precise design, and stratified /adjusted analyses of the gene-gene (haplotypes) and gene-environment interactions are needed.