Inflammation as an Etiologic Agent of Gastric Cancer

Chronic inflammation in the stomach significantly increases the risk of gastric cancer-a deadly disease with a poor prognosis, largely because it is often diagnosed too late. A better understanding of the pathophysiology and molecular mechanisms underlying this increased risk is essential to identify novel diagnostic and therapeutic targets for inflammation-induced carcinogenesis. Gastric epithelial atrophy, a precursor to cancer, can be induced by chemical, autoimmune, and infectious stimuli, primarily infection with Helicobacter pylori. We and others have shown that atrophy can also be induced by the secreted immune products (cytokines) of a type I/Th1 or Th17 immune response. The atrophic phase of gastritis is superseded by a metaplastic, or cellular redifferentiation phase driven by type II (Th2) cytokines. The outcome of this inflammatory sequela is dysplasia of the gastric epithelium; the substrate for multiple types of gastric cancers. Here we summarize our recent findings on Th1/Th17 and Th2 immune responses and their roles in driving gastric atrophy, metaplasia, and carcinogenesis. Importantly, these cytokines and their receptors represent promising therapeutic targets for the prevention and treatment of gastric cancer.