A low vitamin D status is associated with an increased risk of various cancers, such as of colon, breast, prostate and hematological cells. The biologically most active vitamin D metabolite 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) is a high affinity ligand of the transcription factor vitamin D receptor (VDR). 1,25(OH)₂D₃ induces via VDR changes to the epigenome of healthy and neoplastic cells and in this way influences their transcriptome. Ligand-activated VDR binds to more than 10,000 loci within the human genome and affects the transcription of some 1000 target genes in a large proportion of human tissues and cell types. From the evolutionary perspective, the prime role of vitamin D was probably the control of energy metabolism later shifting to modulate innate and adaptive immunity as well as to regulate calcium and bone homeostasis. Since rapidly growing immune and cancer cells both use the same pathways and genes for controlling their proliferation, differentiation and apoptosis, not surprisingly, vitamin D signaling changes these processes also in neoplastic cells. Thus, anti-cancer effects of vitamin D may derive from managing growth and differentiation in immunity. This review provides an update on the molecular basis of vitamin D signaling, i.e., the effects of 1,25(OH)₂D₃ on the epigenome and transcriptome, and its relationship to cancer prevention and therapy.

低维生素 D 状态与各种癌症的风险增加有关，例如结肠癌、乳腺癌、前列腺癌和血液细胞。最具生物学活性的维生素 D 代谢物 1α,25-二羟基维生素 D ₃ (1,25(OH) ₂ D ₃ ) 是转录因子维生素 D 受体 (VDR) 的高亲和力配体。1,25(OH) ₂ D ₃通过诱导VDR 会改变健康细胞和肿瘤细胞的表观基因组，从而影响它们的转录组。配体激活的 VDR 与人类基因组内的 10,000 多个位点结合，并影响大部分人体组织和细胞类型中约 1000 个靶基因的转录。从进化的角度来看，维生素 D 的主要作用可能是控制能量代谢，后来转变为调节先天性和适应性免疫以及调节钙和骨稳态。由于快速生长的免疫细胞和癌细胞都使用相同的途径和基因来控制它们的增殖、分化和凋亡，因此维生素 D 信号传导也会改变肿瘤细胞中的这些过程。因此，维生素 D 的抗癌作用可能源于管理免疫的生长和分化。即，1,25(OH) ₂ D ₃对表观基因组和转录组的影响，以及它与癌症预防和治疗的关系。