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”
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.