ABSTRACT
Epidemiologic and laboratory data suggest that vitamin D protects against inammation and reduces the incidence and severity of many types of cancer. The vitamin D receptor (VDR) is highly expressed in epithelial cells at risk for carcinogenesis (including those resident in the skin, breast, prostate, and colon) and in immune cells that inltrate the tumor microenvironment and participate in tumor surveillance. In epithelial cells, activation of VDR by its ligand, 1,25-dihydroxyvitamin D (1,25D), triggers genomic changes that contribute to maintenance of differentiation via regulation of the cell cycle and apoptosis. Vitamin D also regulates inammatory pathways and modulates cross talk between epithelial cells and immune cells in the context of cancer. Both epithelial and immune cells express the vitamin D metabolizing enzyme cytochrome P450 27B1 (CYP27B1), which enables autocrine generation of 1,25D from the circulating vitamin D metabolite 25-hydroxyvitamin D (25D), critically linking overall vitamin D status with antitumor and anti-inammatory actions. In animal models, dietary vitamin D supplementation, chronic treatment with VDR agonists, and/or VDR deletion alters both inammation and tumorigenesis in the skin, colon, prostate, and breast. Because VDR expression is retained in many human tumors, control of inammatory signaling by vitamin D likely contributes to its ability to reduce cancer development or progression, but clinical data in this area are scarce. Collectively, these observations reinforce the need to further
10.1 Introduction ..........................................................................................................................205 10.2 Vitamin D Biology................................................................................................................206 10.3 Vitamin D and Cancer Overview .........................................................................................206 10.4 Impact of Vitamin D on Immune Cells ................................................................................207 10.5 Introduction to Inammation and Cancer ............................................................................208 10.6 Tissue-Specic Links between Vitamin D, Inammation, and Cancer ...............................208
