Vitamin D as a Potential Therapeutic Option in Cancer Treatment: Is There a Role for Chemoprevention?

Background: Vitamin D (Vit D) serves as a precursor to the potent steroid hormone calcitriol, which regulates numerous genes that control homeostasis, epithelial cell differentiation, proliferation, and apoptosis. Low level of Vit D is implicated in the development and progression of several diseases including bone fractures, cardiovascular disease, diabetes mellitus, and cancers. The present review highlights the role of vitamin D in cancer with a particular emphasis on genetic variants related to Vit D metabolism as well as clinical trials of Vit D supplementation as a potential therapeutic option in the treatment of cancer patients. Methods: Data were collected following an electronic search in the Web of Science, Medline, PubMed, and Scopus databases by using some keywords such as "cancer", "tumor", "malignancy", "vitamin D", "cholecalciferol" and "calcitriol" Results: The collected evidence from the studies revealed a consistent and strong association between Vit D status and cancer risk and survival. The associations between Vit D-related genetic variants and cancer survival support the hypothesis that Vit D may affect cancer outcomes. The mechanisms whereby Vit D reduces cancer risk and increases survival are regulation of cellular differentiation, proliferation and apoptosis as well as decreased angiogenesis in tumor microenvironment and inhibition of metastasis. Conclusion: There is a paucity of evidence-based recommendations for the optimal 25(OH)D levels in patients with cancer and the role of Vit D supplementation for primary or secondary prevention of cancer. Well-designed and sufficiently powered randomized clinical trials are necessary to assess the clinical application of Vit D in enhancing the clinical efficacy of standard and adjuvant chemotherapy regimens.