The interleukin-8-251 A allele is associated with increased risk of noncardia gastric adenocarcinoma in Helicobacter pylori-infected Koreans.

BACKGROUND AND GOALS: Chronic inflammation associated with Helicobacter pylori infection is a risk factor of gastric adenocarcinoma. Interleukin-8 (IL-8) plays an important role in gastric mucosal inflammation induced by H. pylori infection. Recently, studies on the association of genetic polymorphisms of various proinflammatory cytokines with gastric carcinogenesis showed varying results on the basis of the ethnicity. We conducted this study to investigate the association of IL-8-251 A/T polymorphism with gastric carcinogenesis in H. pylori-infected Koreans.

STUDY: The IL-8-251 A/T polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism using DNA from a total of 605 H. pylori-infected subjects; 206 controls, 149 chronic atrophic gastritis and/or intestinal metaplasia, 97 gastric dysplasia, and 153 gastric adenocarcinoma. Degrees of gastric mucosal inflammation and mucosal IL-8 level were also assessed.

RESULTS

The IL-8-251 A carriers showed a higher risk of gastric adenocarcinoma (adjusted odds ratio 2.06, 95% confidence interval 1.16-3.68) than IL-8-251 T/T genotypes. The IL-8-251 A allele was also significantly associated with the degree of neutrophil infiltration, atrophy, and intestinal metaplasia in a younger age group. Among the chronic atrophic gastritis and/or intestinal metaplasia group, mucosal IL-8 level was significantly higher in subjects with IL-8-251 A allele than those with IL-8-251 T/T genotypes (P=0.011).

CONCLUSIONS

The IL-8-251 A allele is associated with higher IL-8 production, more severe inflammation, mucosal atrophy, and intestinal metaplasia than IL-8-251 T/T genotype in H. pylori-infected hosts. The IL-8-251 A allele may also increase the risk of gastric adenocarcinoma through an enhanced inflammatory process in H. pylori-infected Koreans.