Regulation of Gastric Carcinogenesis by Inflammatory Cytokines

Abstract

Chronic inflammation caused by infection with Helicobacter pylori and autoimmune gastritis increases an individual's risk of developing gastric cancer. More than 90% of gastric cancers are adenocarcinomas, which originate from epithelial cells in the chronically inflamed gastric mucosa. However, only a small subset of chronic gastritis patients develops gastric cancer, implying a role for genetic and environmental factors in cancer development. A number of DNA polymorphisms that increase gastric cancer risk have mapped to genes encoding cytokines. Many different cytokines secreted by immune cells and epithelial cells during chronic gastritis have been identified, but a better understanding of how cytokines regulate the severity of gastritis, epithelial cell changes, and neoplastic transformation is needed. This review summarizes studies in both human and mouse models, describing a number of different findings that implicate various cytokines in regulating the development of gastric cancer.

Keywords: ATPase, adenosine triphosphatase; Cytokines; Gastric Cancer; IFN, interferon; IL, interleukin; Inflammation; JAK, Janus-activated kinase; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa B; SPEM, spasmolytic polypeptide-expressing metaplasia; STAT, signal transducer and activator of transcription; Th, T helper.