Vitamin D and cancer: integration of cellular biology, molecular mechanisms and animal models

Scand J Clin Lab Invest Suppl. 2012;243:103-11. doi: 10.3109/00365513.2012.682870.

Abstract

Epidemiologic data suggest that the incidence and severity of many types of cancer inversely correlates with indices of vitamin D status. The vitamin D receptor (VDR) is highly expressed in epithelial cells at risk for carcinogenesis including those resident in skin, breast, prostate and colon, providing a direct molecular link by which vitamin D status impacts on carcinogenesis. Consistent with this concept, activation of VDR by its ligand 1,25-dihydroxyvitamin D (1,25(OH)(2)D) triggers comprehensive genomic changes in epithelial cells that contribute to maintenance of the differentiated phenotype, resistance to cellular stresses and protection of the genome. Many epithelial cells also express the vitamin D metabolizing enzyme CYP27B1 which enables autocrine generation of 1,25(OH)(2)D from the circulating vitamin D metabolite 25-hydroxyvitamin D (25(OH)D), critically linking overall vitamin D status with cellular anti-tumor actions. Furthermore, pre-clinical studies in animal models have demonstrated that dietary supplementation with vitamin D or chronic treatment with VDR agonists decreases tumor development in skin, colon, prostate and breast. Conversely, deletion of the VDR gene in mice alters the balance between proliferation and apoptosis, increases oxidative DNA damage, and enhances susceptibility to carcinogenesis in these tissues. Because VDR expression is retained in many human tumors, vitamin D status may be an important modulator of cancer progression in persons living with cancer. Collectively, these observations reinforce the need to further define the molecular actions of the VDR and the human requirement for vitamin D in relation to cancer development and progression.

MeSH terms

  • Animals
  • DNA Damage
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Neoplasms / etiology*
  • Organ Specificity
  • Receptors, Calcitriol / physiology
  • Vitamin D / physiology*

Substances

  • Receptors, Calcitriol
  • Vitamin D