Vitamin D resistance and colon cancer prevention
Cet article passe en revue les études concernant l'efficacité chimiopréventive de la vitamine D dans le cancer du côlon et fait le point sur les mécanismes limitant cette efficacité
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 pre-clinical 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.
http://carcin.oxfordjournals.org/content/early/2011/12/14/carcin.bgr301.abstract