title: Vitamin D resistance and colon cancer prevention.
abstract: 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.
authors.affiliation: Department of Molecular and Cell Biology, University of Connecticut, 91 North Eagleville Road, U3215, Storrs, CT 06269, USA. charles.giardina@uconn.edu
authors.forename: Charles
authors.initials: C
authors.lastname: Giardina
authors.forename: James P
authors.initials: JP
authors.lastname: Madigan
authors.forename: Cassandra A Godman
authors.initials: CA
authors.lastname: Tierney
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Brenner
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Rosenberg
mesh_terms: D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D018890:Chemoprevention; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020868:Gene Silencing; D006801:Humans; D014807:Vitamin D / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D014807:Vitamin D