title: Inflammation-mediated genomic instability: roles of activation-induced cytidine deaminase in carcinogenesis.
abstract: Chronic inflammation is a strong risk factor for the development of cancer. Many previous studies have demonstrated that a transcriptional factor, nuclear factor (NF)-κB, plays an important role in the association between inflammation and cancer development, particularly tumor promotion and tumor progression. Although it is well recognized that cancer develops via stepwise accumulation of genetic aberrations, the mechanisms underlying the generation of these genetic alterations in normal epithelial cells under inflammatory conditions are not known. We recently demonstrated that pathogenic bacterial or viral factors and the subsequent inflammatory reactions lead to the aberrant expression of a DNA mutator enzyme, activation-induced cytidine deaminase (AID), in various epithelial cells via NF-κB activation, which causes the accumulation of genetic alterations in tumor-related genes. AID activation is widely observed in gastrointestinal tissues with cancer-associated inflammation, such as chronic viral hepatitis, Helicobacter pylori-related gastritis, Barrett's esophagus and inflammatory bowel disease. Furthermore, a deficiency of endogenous AID expression reduces both accumulation of somatic mutations in tumor-related genes and tumor incidence in a mouse model of inflammation-associated cancer development. These findings strongly suggest that AID plays an integral role in inflammation-associated carcinogenesis and is therefore a potential target molecule for the prevention and treatment of cancers.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Marusawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Endo
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D042822:Genomic Instability; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase