Mechanisms by which inflammation may increase intestinal cancer risk in inflammatory bowel disease.
Patients with ulcerative colitis and Crohn's disease are at increased risk of developing intestinal cancers via mechanisms that remain incompletely understood. However, chronic inflammation and repeated events of inflammatory relapse in inflammatory bowel disease (IBD) expose these patients to a number of signals known to have tumorigenic effects including persistent activation of the nuclear factor-kappaB and cyclooxygenase-2/prostaglandin pathways, release of proinflammatory mediators such as tumor necrosis factor-alpha and interleukin-6, and enhanced local levels of reactive oxygen and nitrogen species. These inflammatory signals can contribute to carcinogenesis via 3 major processes: 1) by increasing oxidative stress, which promotes DNA mutagenesis thus contributing to tumor initiation; 2) by activating prosurvival and antiapoptotic pathways in epithelial cells, thereby contributing to tumor promotion; and 3) by creating an environment that supports sustained growth, angiogenesis, migration, and invasion of tumor cells, thus supporting tumor progression and metastasis. The present review integrates clinical and basic research observations in an attempt to provide a comprehensive understanding of how inflammatory processes may contribute to intestinal cancer development in IBD patients.
Department of Biological Sciences and Inflammation Research Network, University of Calgary, Calgary, Alberta, Canada.
Pamela M
PM
O'Connor
Tamia K
TK
Lapointe
Paul L
PL
Beck
Andre G
AG
Buret
D000818:Animals; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015212:Inflammatory Bowel Diseases / Q000150:complications* / Q000276:immunology; D007414:Intestinal Neoplasms / Q000209:etiology* / Q000276:immunology; D051379:Mice; D009154:Mutation; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012306:Risk
D018836:Inflammation Mediators; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species