title: Colonic carcinogenesis in IBD: molecular events.
abstract: Patients with ulcerative colitis (UC) and Crohn's disease (CD) are at increased risk of developing intestinal cancers via mechanisms that remain incompletely understood. Several evidences suggest a causal link between chronic inflammation and the development of cancer in the gastrointestinal tract. In fact, patients with UC are exposed to repeated episodes of inflammation that predispose to various tumorigenic events and the sequence of these events are different from those that contribute to develop a sporadic colorectal cancer. In UC carcinogenesis the early events are represented by DNA methylation that produce an inhibition of onco-suppressor genes, mutation of p53, aneuploidy and microsatellite instability. Hypermethylation of tumor suppressors and DNA mismatch repair gene promoter regions, is an epigenetic mechanism of gene silencing that contributes to tumorigenesis and might represent the first step in inflammatory carcinogenesis. P53 is frequently mutated in the early stages of UC-associated cancer, in 33-67% of patients with dysplasia and in 83-95% of UC related cancer patients. Moreover, aneuploidy is an independent risk factor for forthcoming carcinogenesis in UC Finally, the inconsistency between the high cumulative rate of dysplasia in UC and the relatively lower incidence of invasive cancer raises the question about the mechanisms of immunosurveillance that may prevent malignant progression of neoplasm in the colon in most cases. Co-stimulatory molecule CD80 up-regulation in colonic mucosa in UC dysplasia may be one of these mechanism.
authors.affiliation: Department of Surgical and Gastroenterological Sciences P.G. Cevese, University of Padua, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pozza
authors.forename: Marco
authors.initials: M
authors.lastname: Scarpa
authors.forename: Cesare
authors.initials: C
authors.lastname: Ruffolo
authors.forename: Lino
authors.initials: L
authors.lastname: Polese
authors.forename: Francesca
authors.initials: F
authors.lastname: Erroi
authors.forename: Alessio
authors.initials: A
authors.lastname: Bridda
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Norberto
authors.forename: Mauro
authors.initials: M
authors.lastname: Frego
mesh_terms: D003093:Colitis, Ulcerative / Q000150:complications*; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics; D042822:Genomic Instability; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000473:pathology; D009154:Mutation; D009857:Oncogenes / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial