Vitamin D resistance and colon cancer prevention

Carcinogenesis. 2012 Mar;33(3):475-82. doi: 10.1093/carcin/bgr301. Epub 2011 Dec 16.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anticarcinogenic Agents / administration & dosage
  • Anticarcinogenic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Chemoprevention
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / prevention & control*
  • Drug Resistance, Neoplasm / genetics*
  • Gene Silencing
  • Humans
  • Vitamin D / administration & dosage
  • Vitamin D / pharmacology*


  • Anticarcinogenic Agents
  • Vitamin D