Virulence of Helicobacter pylori infection and gastric cancer: lessons from mouse models

Although discovered only recently, Helicobacter pylori is now considered the prototype for bacteria capable of promoting cancer in humans. Shortly after its isolation and identification in 1982, Marshall and Warren quickly recognized that the human pathogen H. pylori might be responsible for both peptic ulcer disease and gastric cancer. The bacterium was strongly associated with chronic active gastritis, long known to precede cancer, and infection with the organism was endemic in those parts of the world where gastric cancer is prevalent. Given the widespread prevalence of H. pylori infection throughout the world, it was understandable that the proposed link between the bacteria and stomach cancer met with some initial scepticism. Nevertheless, evidence in support of this theory has continued to accumulate and the link between H. pylori and gastric cancer has become less debatable. The H. pylori-gastric cancer connection is now supported by multiple lines of evidence, ranging from clinical epidemiological investigations to prospective observational studies to animal models. However, at a basic level many questions remain. Gastric cancer is the eventual outcome in only 1% of infected individuals; why then does gastric cancer develop in some individuals (but not others), and how does chronic H. pylori infection lead to gastric cancer?