GI system: H. pylori infection and stomach cancer

Helicobacter pylori (H. pylori) is a Gram-negative, microaerophilic bacterium characterized by its ability to survive in highly acidic conditions. Infection with H. pylori can lead to peptic ulcer disease (PUD); in fact, the bacterium is responsible for the development of 70% of gastric ulcers and an estimated 80-95% of duodenal ulcers, which may in turn lead to the development of certain cancers.

Once H. pylori bacteria reach the stomach, they burrow through the protective mucosal layer and adhere to the gastric epithelium, causing local cell destruction and inflammation. H. pylori most commonly colonizes the antrum of the stomach—the distal end of the stomach which connects to the opening to the small intestine, the pyloric sphincter.

Microscopic analysis of stomach mucosa in patients afflicted by PUD reveals a marked destruction in somatostatin-producing D cells (also known as delta cells). The decreased presence of D cells relative to other cell types within the stomach is accompanied by measurable increases in gastric acid production, and a decrease in luminal pH. H. pylori is capable of surviving in these harsh conditions by two mechanisms. First, the mucous layer through which it burrows to reach the epithelial surface is characterized by a more neutral pH than the gastric lumen. Second, the organism is capable of producing the enzyme urease, the effect of which is to produce a more neutral environment in the area immediately surrounding the bacterium.

A strong association between chronic H. pylori infection and the development of gastric cancer has been demonstrated, though few studies have been able to accurately assess whether this risk is more strongly associated with specific subtypes of cancer or their anatomical distribution. A 2001 review of twelve prospective studies attempted to illustrate the association between gastric cancer risk and anatomical distribution (cardia vs. non-cardia) in patients with a known H. pylori infection. The results of this study are shown in Figure 2, which maps the odds ratios (a measure of association wherein a ratio not equal to 1 denotes an association) and 95% confidence intervals for the relationship between cancer development and H. pylori for cardia vs. non-cardia anatomical areas.

Figure 1 Matched odds ratios (ORs) and 95 percent confidence intervals for associations between H. pylori infection and non-cardia cancer (Panel A) and cardia cancer (Panel B). The area of the black squares is proportional to the study size. The white diamond shows the OR value for all studies combined, with the 95% confidence interval represented by horizontal spread.