Inflammation and cancer: an epidemiological perspective.

Many chronic inflammatory conditions increase the risk of cancer in affected tissues. Clinical conditions that involve both inflammation and increased cancer risk include a broad range of immunological disorders, infections (bacterial, helminthic, viral), and chronic chemical and mechanical irritation. For example, the inflammatory bowel diseases, ulcerative colitis and Crohn's disease, predispose to the development of cancers of the large bowel and/or terminal ileum; chronic infection with the bacterium Helicobacter pylori causes atrophic gastritis, dysplasia, adenocarcinoma and an unusual form of gastric lymphoma; and parasitic infection with schistosomes and other trematodes cause cancers of the urinary bladder and the intrahepatic and extrahepatic biliary tract. Chronic reflux of gastric acid and bile into the distal oesophagus causes chemical injury, Barrett's oesophagus and oesophageal adenocarcinoma. Chronic cholecystitis and gallstones predispose to cancer of the gallbladder. Besides these clinical syndromes, subclinical inflammation may promote the development of certain tumours. The expression of COX-2 and lipid mediators of inflammation increases during the multistage progression of these tumours. Non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit COX-2 activity and tumour development in many experimental and clinical settings, are inversely associated with certain cancers in epidemiological studies. Despite their promise, however, anti-inflammatory drugs are not yet recommended for the prevention or treatment of any cancers. Numerous questions must be resolved concerning their molecular and cellular targets of action, efficacy, safety, treatment regimen, indications, and the balance of risks and benefits from treatment in designated patient populations.