Journal Article

Vitamin D resistance and colon cancer prevention

Charles Giardina, James P. Madigan, Cassandra A. Godman Tierney, Bruce M. Brenner and Daniel W. Rosenberg

in Carcinogenesis

Volume 33, issue 3, pages 475-482
Published in print March 2012 | ISSN: 0143-3334
Published online December 2011 | e-ISSN: 1460-2180 | DOI:
Vitamin D resistance and colon cancer prevention

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  • Clinical Cytogenetics and Molecular Genetics


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Observational studies have been largely consistent in showing an inverse association between vitamin D and an individual’s risk of developing colorectal cancer. Vitamin D protection is further supported by a range of preclinical colon cancer models, including carcinogen, genetic and dietary models. A large number of mechanistic studies in both humans and rodents point to vitamin D preventing cancer by regulating cell proliferation. Counterbalancing this mostly positive data are the results of human intervention studies in which supplemental vitamin D was found to be ineffective for reducing colon cancer risk. One explanation for these discrepancies is the timing of vitamin D intervention. It is possible that colon lesions may progress to a stage where they become unresponsive to vitamin D. Such a somatic loss in vitamin D responsiveness bears the hallmarks of an epigenetic change. Here, we review data supporting the chemopreventive effectiveness of vitamin D and discuss how gene silencing and other molecular changes somatically acquired during colon cancer development may limit the protection that may otherwise be afforded by vitamin D via dietary intervention. Finally, we discuss how understanding the mechanisms by which vitamin D protection is lost might be used to devise strategies to enhance its chemopreventive actions.

Journal Article.  6743 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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