Helicobacter pylori-induced enlarged-fold gastritis is associated with increased mutagenicity of gastric juice, increased oxidative DNA damage, and an increased risk of gastric carcinoma.

Abstract

The severe inflammation, increased cell proliferation and marked acid inhibition observed in subjects with Helicobacter pylori-associated enlarged-fold gastritis suggest that enlarged-fold gastritis may be a risk factor for gastric carcinoma. The purpose of the present study was to determine whether a relationship exists between enlarged-fold gastritis and gastric carcinoma. One hundred and thirty-five H. pylori-positive patients with early gastric carcinoma and 141 age- and sex-matched H. pylori-positive controls without gastric carcinoma were involved in the study. The widths of gastric body folds were measured by double-contrast radiographs. The mutagenicity of gastric juice was assayed using the Ames test and Salmonella typhimurium TA-98 or TA-100 with S9-mix. Levels of 8-hydroxydeoxyguanosine (8-OHdG) in gastric mucosa were examined using high-performance liquid chromatographic-electrochemical detection. An upward shift in the distribution of gastric fold widths in H. pylori-positive patients with early gastric carcinoma was found. Enlarged-fold gastritis (fold width >/=5 mm) was observed in 81% of the patients with gastric carcinoma, compared with 46% of H. pylori-positive controls. The odds ratio for gastric carcinoma increased with increasing fold width to a maximum of 35.5 in persons with fold width >/=7 mm. The prevalence of diffuse-type early gastric carcinoma in the body region increased with increasing fold width. The mutagenicity of gastric juice from the patients with enlarged-fold gastritis was significantly higher than that in H. pylori-negative controls and H. pylori-positive patients without enlarged folds. Mucosal 8-OHdG levels in the body region of patients with enlarged-fold gastritis were significantly higher than in H. pylori-negative controls and H. pylori-positive patients without enlarged-fold gastritis. Eradication of H. pylori significantly decreased the mutagenicity of gastric juice and 8-OHdG levels in the gastric mucosa from patients with enlarged-fold gastritis. A significant association is suggested between enlarged-fold gastritis and gastric carcinoma.