Mathematical model of colitis-associated colon cancer

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-kappa B, beta-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. (C) 2012 Elsevier Ltd. All rights reserved.