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.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Giardina C,Madigan JP,Tierney CA,Brenner BM,Rosenberg DW

doi

10.1093/carcin/bgr301

subject

Has Abstract

pub_date

2012-03-01 00:00:00

pages

475-82

issue

3

eissn

0143-3334

issn

1460-2180

pii

bgr301

journal_volume

33

pub_type

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