Colonic carcinogenesis in IBD: Molecular events

Anna Pozza, Marco Scarpa, Cesare Ruffolo, Lino Polese, Francesca Erroi, Alessio Bridda, Lorenzo Norberto, Mauro Frego

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)19-28
Number of pages10
JournalAnnali Italiani di Chirurgia
Volume82
Issue number1
Publication statusPublished - Feb 2011

Keywords

  • Aneuploidy
  • CD80
  • Colonic dysplasia
  • Colorectal cancer
  • Hypermethilation
  • Immunosurveillance
  • p53
  • Ulcerative colitis

ASJC Scopus subject areas

  • Surgery

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