Vitamin D and the risk for cancer: A molecular analysis

Uncontrolled overgrowth of cells, such as in cancer, is an unavoidable risk in life that affects nearly every second individual in industrialized countries. However, in part this risk can be controlled through lifestyle adjustments, such as the avoidance of smoking, unhealthy diet, obesity, physical inactivity and other cancer risk factors. A low vitaminD status is a risk in particular for cancers of colon, prostate, breast and leukocytes. VitaminD₃ is produced non-enzymatically, when the cholesterol precursor 7-dehydrocholesterol is exposed to UV-B from sunlight, i.e., all cholesterol synthesizing species, including humans, can make vitaminD₃. VitaminD endocrinology started some 550million years ago, when the metabolite 1α,25-dihydroxyvitaminD₃ and the transcription factor vitaminD receptor teamed up for regulating the expression of hundreds of target genes in a multitude of different tissues and cell types. Initially, these genes were focused on the control of energy homeostasis, which later also involved energy-demanding innate and adaptive immunity. Rapidly growing cells of the immune system as well as those of malignant tumors rely on comparable genes and pathways, some of which are modulated by vitaminD. Accordingly, vitaminD has anti-cancer effects both directly via controling the differentiation, proliferation and apoptosis of neoplastic cells as well as indirectly through regulating immune cells that belong to the microenvironment of malignant tumors. This review discusses effects of vitaminD on the epigenome and transcriptome of stromal and tumor cells, inter-individual variations in vitaminD responsiveness and their relation to the prevention and possible therapy of cancer.