Gastric cancer: laboratory bench to clinic

Abstract

Gastric cancer is the second most common cause of cancer-related mortality worldwide and the 14th overall cause of death. Detection of disease usually occurs at an advanced stage and overall survival rates for gastric cancer are poor. Our current model for gastric cancer progression clearly maintains Helicobacter infection as the primary inducer of gastric metaplastic and neoplastic disease. Helicobacter pylori is a ubiquitous organism, infecting more than half the world's population. It has been suggested that this infection directly contributes to the formation of gastric cancer in up to 80% of cases; however, gastric malignancy develops in only a subset (< 1%) of infected patients. Therefore, predisposition to Helicobacter-associated gastric cancer is most likely multifactorial, including the interaction of bacterial, host and environmental components. Our understanding of how the organism interacts with the gastric mucosa and synergizes with dietary and other environmental factors to induce malignant mucosal changes is evolving. Indeed, H. pylori has direct effects on the gastric mucosa, but the major factor in disease progression appears to be a robust host Th1 immune response in the setting of a permissive environment. In combination, these factors predispose to the formation of atrophy, metaplasia and gastric cancer. Understanding the interaction of the bacterium with the host and the environment can potentially identify patients most at risk. Identifying potentially removable factors (in addition to H. pylori infection) in the acquisition and progression of neoplastic disease may provide targets for early intervention and prevention strategies.