Vitamin D endocrine system in breast cancer

Abstract

Vitamin D is a steroid hormone of great importance in the human body. It is produced in the skin from 7-dehydrocholesterol, upon UV radiation. In order to exert its functions, vitamin D has to be hydroxylated (via CYP27A1 and CYP27B1 hydroxylases), which is followed by its interaction with the vitamin D receptor (VDR) or retinoic acid-related orphan receptors α or γ (RORα and RORγ). By binding with the vitamin D response elements (VDRE) located in the promoter regions, the vitamin D ligand-receptor complex may regulate vitamin D-related genes. Recently, vitamin D has acquired a great interest for its plausible association with cancer development. This review discusses the potential role of vitamin D, its analogues, and enzymes involved in its metabolism with breast cancer incidence and outcome. According to the literature, alterations in the vitamin D endocrine system, both at the mRNA and protein level, have an impact on breast cancer incidence and prognosis. Moreover, specific enzymes participating in vitamin D metabolism may serve as therapeutic targets. Notably, treatment with vitamin D analogues also gives promising results in experimental research. However, given the fact that breast cancer is heterogenous disease, further studies are needed to thoroughly elucidate the potential of vitamin D and enzymes involved in its metabolism in breast cancer development, progression and therapy. Therefore, plausible effects of vitamin D in cancer therapy or prevention have been the principal aim of numerous studies.

Polymorphisms in VDR, CYP27B1, CYP2R1, GC and CYP24A1 Genes as Biomarkers of Survival in Non-Small Cell Lung Cancer: A Systematic Review

“…However, only one study found a significant relationship between this polymorphism and OS. Heist et al report that in 294 patients of Caucasian origin (from USA) with advanced NSCLC, in the multivariate Cox regression model, patients carrying the CT and TT genotypes showed a higher risk of death than those carrying the CC genotype ( p = 0.04; HR = 1.32; 95% CI = 0.98–1.77; CT vs. CC, and p = 0.04; HR = 1.41; 95% CI = 0.96–2.07; TT vs. CC) [ 23 ]. The influence of FokI on PFS was assessed in three studies.…”

“…These VDREs enable the expression of a host of genes, which are related to key processes in the inception and development of cancer. This evidence suggests that low serum calcidiol levels or dysfunctionality of the vitamin may favor carcinogenesis, due to the presence of single-nucleotide polymorphisms (SNPs) in the genes that participate in vitamin D metabolism ( GC or VDBP , VDR , CYP2R1 , CYP27B1 , and CYP24A1 ) [ 22 , 23 , 24 ]. There are studies that have evaluated the influence of SNP prevalence in these genes associated with risk, survival, progression-free survival, and response to platinum-based chemotherapy in lung cancer, specifically NSCLC [ 10 , 14 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ].…”

Prevalence and Relevance of Vitamin D Deficiency in Newly Diagnosed Breast Cancer Patients: A Pilot Study

“…The vitamin D receptor is commonly expressed in breast tissues, as well as in breast cancer cells [ 33 ]. It could be proven that vitamin D binds to vitamin D response elements of the promoter region of cells and thus regulates vitamin D-dependent genes [ 7 ]. A possible explanation of how vitamin D might affect breast cancer biology might be the tumor suppressive effects of vitamin D receptor catabolism, as a defect in the vitamin D receptor (e.g., CYP27B1 and CYP24A1 regulation) led to decreased signaling [ 33 ].…”

“…By modulating IncRNA, vitamin D could have a protective effect on the development of breast cancer [ 34 ]. However, by now these results could mostly be shown in vitro and in animal experiments, not in clinical trials [ 7 , 8 , 9 ]. Thus, a general benefit of vitamin D substitution in cancer patients or influence on therapy success and outcome could not yet been proven [ 1 , 35 ].…”

“…Vitamin D and its possible role in cancer development has been very controversial in recent years [ 7 ]. The important role of vitamin D in cell differentiation, as well as anti-inflammatory effects and antiproliferative effects, is already known [ 8 ].…”