Bacteria in the Aetio-pathogenesis of Gastric Cancer: A Review

Abstract

Severe atrophic gastritis, a precursor lesion of gastric carcinoma, is connected, in two different ways, with intragastric bacterial colonization: (1) in advanced atrophic body gastritis (type A), achlorhydria or severe hypochlorhydria leads to bacterial overgrowth with aerobic and anaerobic flora enabling the conversion of nitrate to nitrite and further to N-nitroso compounds; (2) the newly re-discovered Helicobacter pylori is probably one of the major causes of chronic atrophic antral gastritis (type B). Both types of bacteria may be involved in the pathogenesis of multifocal gastritis (type AB). In the western world, achlorhydric atrophic gastritis is not only found in pernicious anaemia but is latent in about 2 to 6% of the general population. In one study from the Mayo Clinic, about one-third of consecutive gastric carcinomas were present in achlorhydric stomachs, the remainder in acid-secretors. Apart from the N-nitroso compounds, other carcinogenic mechanisms may be active in type A gastritis: elevated serum gastrin; altered cell turnover; immunologic and hereditary traits. The association of H. pylori with gastric carcinoma is mainly based on circumstantial evidence: (i) epidemiological studies indicate a moderately increased risk for gastric cancer in H. pylori-positive subjects compared with H. pylori-negative; (ii) in the presence of H. pylori intragastric levels of the anti-oxidant ascorbic acid are lowered; (iii) H. pylori seems to be linked to mucosal atrophy and intestinal metaplasia; (iv) recent follow-up studies show a significant development of atrophic gastritis in H. pylori-positive patients compared to H. pylori-negative. However, with respect to a multitude of confounding factors in the epidemiological studies and to the equivocies of the morphological and biochemical findings, further prospective and controlled studies of H. pylori in gastric carcinogenesis have to be awaited. In conclusion, the aetio-pathogenetic role of intragastric bacterial growth (H. pylori and/or other bacterial flora) in gastric cancer is suggestive but has to be studied more widely before large-scale propaganda and medical intervention are justified. In this context, reliable diagnostic methods are mandatory concerning the identification of potential risk factors, such as atrophic gastritis, intragastric bacteria, and N-nitroso compounds.

Key Words:

• Achlorhydria
• atrophic gastritis
• bacterial growth in the stomach
• gastric cancer
• Helicobacter pylori
• intestinal metaplasia
• N-nitroso compounds