title: Mathematical model of colitis-associated colon cancer.
abstract: As a result of chronic inflammation of their colon, patients with ulcerative colitis or Crohn's disease are at risk of developing colon cancer. In this paper, we consider the progression of colitis-associated colon cancer. Unlike normal colon mucosa, the inflammed colon mucosa undergoes genetic mutations, affecting, in particular, tumor suppressors TP53 and adenomatous polyposis coli (APC) gene. We develop a mathematical model that involves these genes, under chronic inflammation, as well as NF-κB, β-catenin, MUC1 and MUC2. The model demonstrates that increased level of cells with TP53 mutations results in abnormal growth and proliferation of the epithelium; further increase in the epithelium proliferation results from additional APC mutations. The model may serve as a conceptual framework for further data-based study of the early stage of colon cancer.
authors.affiliation: Mathematical Biosciences Institute, The Ohio State University, Columbus, OH 43210, USA. lo.75@mbi.osu.edu
authors.forename: Wing-Cheong
authors.initials: WC
authors.lastname: Lo
authors.forename: Edward W
authors.initials: EW
authors.lastname: Martin
authors.forename: Charles L
authors.initials: CL
authors.lastname: Hitchcock
authors.forename: Avner
authors.initials: A
authors.lastname: Friedman
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D045744:Cell Line, Tumor; D002908:Chronic Disease; D003092:Colitis / Q000150:complications* / Q000473:pathology; D003110:Colonic Neoplasms / Q000150:complications* / Q000235:genetics / Q000473:pathology; D003198:Computer Simulation; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology; D008954:Models, Biological; D018396:Mucin-1 / Q000378:metabolism; D055262:Mucin-2 / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051176:beta Catenin / Q000378:metabolism
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D018396:Mucin-1; D055262:Mucin-2; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin