Gastric Carcinoma and Helicobacter pylori Infection: Role of Nitric Oxide and Inflammatory Cytokines in Gastric Carcinogenesis

Recent studies have shown that Helicobacter pylori infection is etiologically and experimentally associated with gastric carcinoma. However, the role of H. pylori in carcinogenesis has not been clarified. H. pylori infection leads to sustained production of the reactive nitrogen species that cause DNA damage. We discuss hypotheses related to possible mechanisms of action of H. pylori in human gastric carcinogenesis and tumor progression, especially the role of reactive nitrogen species and inflammatory cytokines. Immunohistochemical analysis revealed that the expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine in the gastric mucosa was significantly higher in H. pylori-positive subjects than in H. pylori-negative subjects. Among the H. pylori-positive patients, the expression of iNOS and nitrotyrosine in the gastric mucosa was significantly higher in those who developed gastric carcinoma than in the controls. H. pylori with cagA gene induces inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF). IL-1 and TNF may cause overexpression of iNOS and nitrotyrosine in gastric mucosa, and IL-8 may promote tumor growth through its angiogenic activity.