Inflammatory colonic carcinogenesis: A review on pathogenesis and immunosurveillance mechanisms in ulcerative colitis

Marco Scarpa, Ignazio Castagliuolo, Carlo Castoro, Anna Pozza, Melania Scarpa, Andromachi Kotsafti, Imerio Angriman

Research output: Contribution to journalArticle

Abstract

Ulcerative colitis (UC) is characterized by repeated flare-ups of inflammation that can lead to oncogenic insults to the colonic epithelial. UC-associated carcinogenesis presents a different sequence of tumorigenic events compared to those that contribute to the development of sporadic colorectal cancer. In fact, in UC, the early events are represented by oxidative DNA damage and DNA methylation that can produce an inhibition of oncosuppressor genes, mutation of p53, aneuploidy, and microsatellite instability. Hypermethylation of tumor suppressor and DNA mismatch repair gene promoter regions is an epigenetic mechanism of gene silencing that contribute to tumorigenesis and may represent the first step in inflammatory carcinogenesis. Moreover, p53 is frequently mutated in the early stages of UC-associated cancer. Aneuploidy is an independent risk factor for forthcoming carcinogenesis in UC. Epithelial cell-T-cell cross-talk mediated by CD80 is a key factor in controlling the progression from low to high grade dysplasia in UC-associated carcinogenesis.

Original languageEnglish
Pages (from-to)6774-6785
Number of pages12
JournalWorld Journal of Gastroenterology
Volume20
Issue number22
DOIs
Publication statusPublished - 2014

Keywords

  • Carcinogenesis
  • Colorectal cancer
  • Immune surveillance
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

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