Helicobacter pylori: the link with gastric cancer

Gastric cancer is the world's overall second most common cancer, and carries a bad prognosis. In the Correa model of gastric carcinogenesis, environmental factors (salt, nitrate, a lack of vitamin C and beta-carotene, bile reflux, bacterial overgrowth in atrophic gastritis with nitrosamine formation) are related to the evolution from normal gastric tissue through superficial gastritis, multifocal atrophic gastritis, intestinal metaplasia and dysplasia to carcinoma. The incidence of H. pylori decreases with progressing preneoplastic lesions. In several studies, the prevalence of H. pylori was elevated in patients with gastric cancer, with a trend for a higher prevalence in intestinal type gastric cancer vs diffuse type. Family members of patients with gastric adenocarcinoma have a higher H. pylori prevalence than controls; patients infected with H. pylori have more family members with gastric cancer. Several epidemiological studies showed a higher H. pylori prevalence in regions or populations with high gastric cancer risk vs low-risk populations. Large-scale studies in China and Europe showed a correlation between H. pylori seroprevalence and gastric cancer incidence and mortality. Three prospective nested case-control studies showed that infection with H. pylori increased the risk of further development of gastric adenocarcinoma, showing that H. pylori infection precedes the development of gastric cancer. Several pathways can be identified explaining the association between H. pylori and gastric adenocarcinoma. We showed that gastric cell proliferation is increased in parallel with inflammation. The ascorbic acid concentrating mechanism is abolished in gastritis. Ammonia, generated by H. pylori's urease, gives rise to gastric mucosal atrophy. We showed that salt increases the gastric cell proliferation only in H. pylori-infected individuals. The organism's toxin may play a role in gastric cancer. Besides H. pylori, other environmental factors are important in determining the gastric cancer risk. For instance, we showed that in Belgium, Maghreb immigrants have a high prevalence of H. pylori infection but a low prevalence of intestinal metaplasia and gastric cancer. Gastric lymphoma is rare (about 5% of all gastric tumours), but its incidence is steadily increasing. It was shown that H. pylori also increases the risk for low-grade as well as high-grade gastric lymphoma. Eradication of H. pylori has been shown to cure several cases of unequivocally proven gastric low-grade lymphoma.(ABSTRACT TRUNCATED AT 400 WORDS)