The role of inflammation in gastric tumorigenesis

Inflammation promotes cancer development through a variety of mechanisms. Helicobacter pylori infection induces atrophic gastritis, which causes mucous cell metaplasia-spasmolytic polypeptide-expressing metaplasia (SPEM), followed by dysplastic change and gastric cancer development. Mouse model studies have indicated that the cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) pathway together with Toll-like receptor/MyD88 innate immune response induces the generation of an inflammatory microenvironment, which plays an important role in gastric tumorigenesis in combination with genetic alterations in tumor cells. Inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-11 support the tumorigenicity of cancer cells through a variety of mechanisms including the activation of reactive oxygen species signaling and dysregulation of microRNA expression. Accordingly, in this chapter, we will provide an overview of how the regulation of inflammatory pathways by targeting COX-2, cytokines, and their downstream pathways will be an effective preventative strategy against gastric cancer development.