Helicobacter pylori-induced apoptosis in pathogenesis of gastric carcinoma

Background: Despite a possible role of Helicobacter pylori in gastric carcinoma (GC), its pathogenesis is not clear. There is scanty data on apoptosis in GC in relation to H. pylori and CagA antibody. Therefore, we studied gastric epithelial apoptosis in GC and non-ulcer dyspepsia (NUD) with or without H. pylori infection, and the degree of apoptosis in relation to CagA antibody status. Methods: 20 patients each with GC and NUD were investigated for H. pylori using rapid urease test (RUT), IgG anti- H. pylori and anti-CagA antibodies, histology of endoscopically normal-looking mucosa for H. pylori , intestinal metaplasia (IM), and apoptosis using TUNEL assay. Positivity to one tissue-based (RUT or histology) and one serology based (anti- H. pylori or CagA IgG) test was taken as diagnostic of active H. pylori infection, and negative result in both tissue-based tests suggested its absence. Results: Patients with GC more often had anti- H. pylori IgG (16 of 20 vs. 8 of 20; p=0.02) and a trend towards higher apoptotic index (AI) (48.6 [19.2 to 71.7] vs. 41.4 [11.7 to 63.6]; p=0.06) than NUD. AI was higher in GC (66.7 [57.5 to 71.7] vs. 32.6 [19.2 to 39.8]; p <0.0001) and NUD (58.6 [50.7 to 63.6] vs. 24.4 [11.7 to 32.2]; p<0.0001) infected with H. pylori than in those without infection. AI was also higher in GC than in NUD with H. pylori infection (66.7 [57.5 to 71.7] vs. 58.6 [50.7 to 63.6]; p= 0.01). Four of the 20 patients with GC and none with NUD had IM (p=ns). There was no difference in AI in relation to CagA antibody. AI positively correlated with patients' age in presence of H. pylori infection (correlation coefficient = 0.5, p=0.03) but not in its absence. Conclusion: Exaggerated apoptosis may play a role in H. pylori- mediated gastric diseases including carcinogenesis. AI increases with aging in patients infected with H. pylori.