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

Background and Aim:  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. Methods:  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. Results:  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. Conclusion:  A significant association is suggested between enlarged-fold gastritis and gastric carcinoma.