The Role of inflammation in Colorectal Cancer

Chronic inflammation has been implicated as playing an essential role in a number of human cancers including colorectal cancer (CRC).  Chronic inflammation is a condition in which the body's immune system's inflammatory response is turned on.  When the inflammatory response is prevalent in the intestines, powerful factors are secreted including: Interleukin-6 (IL-6), tumor necrosis factor (TNF-α), IL-23 and reactive oxygen species.  All these may act in consort to create a microenvironment that can lead to accelerated DNA damage in the intestinal epithelia and thereby increase the likelihood of leading to CRC as is demonstrated by the discovery of a colitis-associated CRC.

 

Furthermore, within the lumen of the colon, literally trillions of bacteria coexist in an environment referred to as the "microbiota."  These bacteria live in close proximity to the epithelial cells that line the colon.  From this information, the question naturally arises, "Do these bacteria, under the right conditions participate in some way with the cancer-causing process – carcinogenesis?"

 

In attempt to determine the answer to his question, Janelle C. Arthur and her colleagues at the Department of Medicine at the University of North Carolina at Chapel Hill studied the association of the microbiota, chronic inflammation and the onset of colon cancer in mice with a genetic susceptibility to colitis.  Their findings can be summarized in the following way:

 

·       Monocolonization  of the experimental animal's gut with Escherichia coli (E. coli) NC101 promoted the development of CRC in azomethane treated animals – azomethane is a potent carcinogen

·         Deletion of the particular strain of E-coli – polyketide synthase (pks+) strain known to have a deleterious impact on host genes, genotoxic, decrease the amount of invasive tumors

·         Pks+ E. coli are found in a significant percentage of human patients with inflammatory bowel disease and CRC.

 

These data demonstrate that within the scope of the mouse model, colitis, as an example of chronic inflammation in the gut, can promote CRC by altering the microbial composition of the intestinal microbiota.  In addition, these findings may have direct application to the understanding of the development of human CRC.