Colon carcinogenesis in inflammatory bowel disease

Steven H. Itzkowitz, Bruce Greenwald, Stephen J. Meltzer

Research output: Contribution to journalReview articlepeer-review

Abstract

Colon cancers arising in the setting of chronic inflammatory bowel disease (IBD) share only some of the clinicopathological features with sporadic colon cancers. Whereas much is known about the molecular alterations involved in sporadic colon cancer, less is known in this regard with respect to colitis‐associated neoplasms. Of the phenotypic alterations that have been most widely studied, increases in sialomucin and decreases in sialic acid O‐acetylation appear to correlate with malignant progression in IBD. These mucin alterations, exemplified by sialosyl‐Tn antigen, suggest that small intestinal metaplasia occurs as part of the carcinogenic process. At the molecular genetic level, genomic instability and clonal evolution, as evidenced by abnormal DNA content (aneuploidy) are associated with malignant progression. The activation of specific protooncogenes (k‐ras, c‐src) and the loss or mutation of certain tumor suppressor genes (p53, APC) occur in colitis‐associated colon neoplasms, although the frequency and chronology of these alterations may differ from that of sporadic carcinogenesis. Microsatellite instability also occurs during colitis‐associated carcinogenesis, but mutations in DNA mismatch repair genes often associated with this molecular alteration have not yet been described. Additional research will be required to elucidate the basic pathobiology of carcinogenesis in IBD and to determine how this knowledge can be used to influence clinical management of patients.

Original languageEnglish (US)
Pages (from-to)142-158
Number of pages17
JournalInflammatory bowel diseases
Volume1
Issue number2
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

Keywords

  • APC gene
  • Allelic deletion
  • Carbohydrate antigens
  • Carcinogenesis
  • Clonal evolution
  • Colon carcinoma
  • Crohn's colitis
  • DNA aneuploidy
  • DNA repair
  • Lectins
  • Microsatellite instability
  • Mucin
  • Oncogenes
  • O‐acetylation
  • Prognostic markers
  • Sialomucin
  • Small intestinal metaplasia
  • Tumor suppressor genes
  • Ulcerative colitis
  • c‐src
  • k‐ras
  • p53 gene

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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