Special Issue: Inflammatory Bowel Diseases and Intestinal Epithelial Stem Cells

The development of colorectal cancer caused by chronic inflammatory bowel disease (IBD) is the representative example of inflammation-associated carcinogenesis. The mechanism underlying the development of colorectal cancers through chronic inflammation, however, is not known. Activation-induced cytidine deaminase (AID) was originally identified as an inducer of somatic hypermutation in the immunoglobulin gene. We recently demonstrated that the mutagenic activity of AID expression links colonic inflammation to the development of colitis associated colorectal cancers. Immunohistochemistry revealed enhanced expression of endogenous AID protein not only in the inflamed colonic mucosa of ulcerative colitis patients, but also in tumor lesions of colitis-associated colorectal cancers. Pro-inflammatory cytokine TNF-α and/or T helper cell-2driven cytokines IL-4 and IL-13 induced aberrant expression of AID in human colonic epithelial cells. In vivo, aberrant AID expression in the inflamed colon is associated with the accumulation of somatic mutations in tumor suppressor Trp53 gene, and AID deficiency resulted in a reduced incidence of colitis-associated colon cancers. These findings suggested that pro-inflammatory cytokine-mediated aberrant expression of AID in colonic epithelial cells plays a role as a genotoxic factor that enhances genetic instability during chronic colonic inflammation, leading to colitisassociated colorectal cancer development. Rec./Acc.12/15/2011,pp67-71