Chronic inflammation: a common and important factor in the pathogenesis of neoplasia

A causal link between chronic inflammation and carcinogenesis is explored by reviewing illustrative examples of specific cancers and causal agents and mechanisms. The causal agents or pathologic conditions include microbial agents, gastroesophageal reflux, chronic cholecystitis and cholelithiasis, inflammatory bowel disease, and specific agents that cause chronic obstructive or diffuse interstitial lung disease. The proportion of total cancer deaths attributable to infectious agents is estimated to be about 20% to 25% in developing countries and 7% to 10% in more industrialized countries. Recurrent or persistent inflammation may induce, promote, or influence susceptibility to carcinogenesis by causing DNA damage, inciting tissue reparative proliferation, and/or creating a stromal "soil" that is enriched with cytokines and growth factors. Future research on the complex cascade of cellular and humoral factors participating in the chronic inflammatory process will further understanding of the pathogenesis of various cancers and potentially provide a rationale for targeted chemopreventive interventions.