Chronic inflammation has been seen, both experimentally and epidemiologically, to be an important factor in tumor development. Chronic inflammation can be caused by viral or bacterial infections, autoimmune diseases and inflammatory conditions of unknown origins. It has been shown that mutation of key inflammatory control genes is associated with a higher risk of cancer progression, and markers of inflammation correlate with a worse prognosis for cancer patients. Inflammation seems to lead to the development of cancer because of the activities of leukocytes, including the production of proteins that alter the behavior of target cells (cytokines and chemokines), stimulation of blood vessel growth (angiogenesis) and tissue remodeling. Immune cells also produce oxygen radicals that can cause mutations in DNA.
Inflammation can both induce carcinogenesis and lead to progression and metastasis. The activation of a specifictranscription factor,NF-kB, by pro-inflammatory cytokines has been shown to produce a more aggressive cancer phenotype including resistance to normal growth control mechanisms, angiogenetic capability and metastasis. Tumor associated macrophages (TAM), are also associated with the inflammatory pathway, have been observed to produce pro-angiogenic factors and recruit blood vessels early in tumor development. TAM also increase the growth rate of tumor cells and cause the dissolution of the connective tissue matrix surrounding the tumor, enabling tumor growth and spread. (1)
There are several cancer types associated with chronic inflammatory conditions, including; colon cancer and inflammatory bowel disease, liver cancer and hepatitis C, bladder or colon cancer and schistosomiasis (a chronic parasitic infection) and stomach cancer and H. pylori infection. (2)