Environment-gene interactions in intestinal cancer

Leonard H. Augenlicht, Barbara G. Heerdt, John M. Mariadason, WanCai Yang, Andrew J. Wilson, Alessandra Fragale, Anna Velcich

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Only 5-10% of all colorectal cancer in the United States can be directly attributed to inheritance of genetic predisposition for tumor development. Thus, the vast majority of colorectal cancer is classified as sporadic, and in these patients environmental factors - particularly the diet - play a major role in determining the probability of tumor formation and its progression. Investigations of how dietary components interact with genetic factors in cancer development have been extremely productive in terms of understanding the subtle and complex mechanisms that maintain homeostasis of the intestinal mucosa, and how perturbations in these mechanisms cause disease. We have found that the cyclin-dependent kinase inhibitor p21WAF1/cip1 plays a major role in regulating several aspects of mucosal homeostasis and the response to dietary and pharmacologic modulators of tumorigenesis; that disruption of lineages of differentiation of intestinal epithelial cells are intimately involved in tumor formation; and that important pathways that contribute to normal homeostasis and cancer development may be coordinately regulated by mitochondrial function, with the mitochondrial membrane potential playing a key role. Several lines of evidence from our work have also suggested that intestinal epithelial cells have adapted to the environment that they usually encounter. This renders the cells competent to efficiently utilize factors in the intestinal lumen in normal metabolic and signaling pathways that contribute to homeostasis.

Original languageEnglish (US)
JournalEuropean Journal of Cancer Prevention
Volume11
Issue numberSUPPL. 2
StatePublished - Aug 2002

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Intestinal Neoplasms
Gene-Environment Interaction
Homeostasis
Neoplasms
Colorectal Neoplasms
Epithelial Cells
Cyclin-Dependent Kinases
Mitochondrial Membrane Potential
Intestinal Mucosa
Genetic Predisposition to Disease
Metabolic Networks and Pathways
Carcinogenesis
Diet

Keywords

  • Colon cancer
  • Differentiation
  • Fatty acids
  • Genomics
  • Mitochondria
  • Mucin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Augenlicht, L. H., Heerdt, B. G., Mariadason, J. M., Yang, W., Wilson, A. J., Fragale, A., & Velcich, A. (2002). Environment-gene interactions in intestinal cancer. European Journal of Cancer Prevention, 11(SUPPL. 2).

Environment-gene interactions in intestinal cancer. / Augenlicht, Leonard H.; Heerdt, Barbara G.; Mariadason, John M.; Yang, WanCai; Wilson, Andrew J.; Fragale, Alessandra; Velcich, Anna.

In: European Journal of Cancer Prevention, Vol. 11, No. SUPPL. 2, 08.2002.

Research output: Contribution to journalArticle

Augenlicht, LH, Heerdt, BG, Mariadason, JM, Yang, W, Wilson, AJ, Fragale, A & Velcich, A 2002, 'Environment-gene interactions in intestinal cancer', European Journal of Cancer Prevention, vol. 11, no. SUPPL. 2.
Augenlicht LH, Heerdt BG, Mariadason JM, Yang W, Wilson AJ, Fragale A et al. Environment-gene interactions in intestinal cancer. European Journal of Cancer Prevention. 2002 Aug;11(SUPPL. 2).
Augenlicht, Leonard H. ; Heerdt, Barbara G. ; Mariadason, John M. ; Yang, WanCai ; Wilson, Andrew J. ; Fragale, Alessandra ; Velcich, Anna. / Environment-gene interactions in intestinal cancer. In: European Journal of Cancer Prevention. 2002 ; Vol. 11, No. SUPPL. 2.
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