The Role of Vitamin D in Reducing Cancer Risk and Progression

Overview

Journal Nat Rev Cancer

Specialty Oncology

Date 2014 Apr 8

PMID 24705652

Citations 590

Authors

David Feldman

Aruna V Krishnan

Srilatha Swami

Edward Giovannucci

Brian J Feldman

Affiliations

Soon will be listed here.

Abstract

Vitamin D is not really a vitamin but the precursor to the potent steroid hormone calcitriol, which has widespread actions throughout the body. Calcitriol regulates numerous cellular pathways that could have a role in determining cancer risk and prognosis. Although epidemiological and early clinical trials are inconsistent, and randomized control trials in humans do not yet exist to conclusively support a beneficial role for vitamin D, accumulating results from preclinical and some clinical studies strongly suggest that vitamin D deficiency increases the risk of developing cancer and that avoiding deficiency and adding vitamin D supplements might be an economical and safe way to reduce cancer incidence and improve cancer prognosis and outcome.

Citing Articles

Enzyme-responsive vitamin D-based micelles for paclitaxel-controlled delivery and synergistic pancreatic cancer therapy.

Peixoto D, Ravasco J, Blanco-Fernandez B, Veiga F, Concheiro A, Conde J Mater Today Bio. 2025; 31:101555.

PMID: 40026626 PMC: 11869029. DOI: 10.1016/j.mtbio.2025.101555.

Gene expression associated with endocrine therapy resistance in estrogen receptor-positive breast cancer.

Jones V, Yin H, Yuan Y, Wang Y, Li S, Aljaber D Sci Rep. 2025; 15(1):7220.

PMID: 40021703 PMC: 11871144. DOI: 10.1038/s41598-025-89274-9.

Hypovitaminosis D in patients with oral leukoplakia: insights from a cross-sectional study.

Maturana-Ramirez A, Aitken-Saavedra J, Mora-Ferraro D, Rojas-Zuniga G, Espinoza-Santander I, Rojas-Alcayaga G Front Oncol. 2025; 15:1522726.

PMID: 39980554 PMC: 11839706. DOI: 10.3389/fonc.2025.1522726.

Vitamin D derivatives inhibit mesenchymal transition of mesothelial cells and mitigate peritoneal dissemination of ovarian cancer.

Fujita K, Hayashi M, Yoshihara M, Nomura S, Kitami K, Miyamoto E Med Mol Morphol. 2025; .

PMID: 39964447 DOI: 10.1007/s00795-025-00424-4.

Liposomal encapsulation of cholecalciferol mitigates toxicity and delays tumor growth.

Ezcurra-Hualde M, Zalba S, Bella A, Arrizabalaga L, Risson A, Garcia-Fuentes R Front Immunol. 2025; 16:1529007.

PMID: 39931063 PMC: 11807986. DOI: 10.3389/fimmu.2025.1529007.

References

Gonzalez-Sancho J, Alvarez-Dolado M, Munoz A . 1,25-Dihydroxyvitamin D3 inhibits tenascin-C expression in mammary epithelial cells. FEBS Lett. 1998; 426(2):225-8. DOI: 10.1016/s0014-5793(98)00348-2. View

Srinivas S, Feldman D . A phase II trial of calcitriol and naproxen in recurrent prostate cancer. Anticancer Res. 2009; 29(9):3605-10. View

Holt S, Kwon E, Peters U, Ostrander E, Stanford J . Vitamin D pathway gene variants and prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 2009; 18(6):1929-33. PMC: 2743676. DOI: 10.1158/1055-9965.EPI-09-0113. View

Trump D, Deeb K, Johnson C . Vitamin D: considerations in the continued development as an agent for cancer prevention and therapy. Cancer J. 2010; 16(1):1-9. PMC: 2857702. DOI: 10.1097/PPO.0b013e3181c51ee6. View

Newmark H, Yang K, Kurihara N, Fan K, Augenlicht L, Lipkin M . Western-style diet-induced colonic tumors and their modulation by calcium and vitamin D in C57Bl/6 mice: a preclinical model for human sporadic colon cancer. Carcinogenesis. 2008; 30(1):88-92. PMC: 2722141. DOI: 10.1093/carcin/bgn229. View

Ray R, Banks M, Abuzahra H, Eddy V, Persons K, Lucia M . Effect of dietary vitamin D and calcium on the growth of androgen-insensitive human prostate tumor in a murine model. Anticancer Res. 2012; 32(3):727-31. PMC: 4681513. View

Lopes N, Sousa B, Martins D, Gomes M, Vieira D, Veronese L . Alterations in Vitamin D signalling and metabolic pathways in breast cancer progression: a study of VDR, CYP27B1 and CYP24A1 expression in benign and malignant breast lesions. BMC Cancer. 2010; 10:483. PMC: 2945944. DOI: 10.1186/1471-2407-10-483. View

Choudhury S, Almendro V, Merino V, Wu Z, Maruyama R, Su Y . Molecular profiling of human mammary gland links breast cancer risk to a p27(+) cell population with progenitor characteristics. Cell Stem Cell. 2013; 13(1):117-30. PMC: 3703476. DOI: 10.1016/j.stem.2013.05.004. View

Kupferschmidt K . Uncertain verdict as vitamin D goes on trial. Science. 2012; 337(6101):1476-8. DOI: 10.1126/science.337.6101.1476. View

10.

Abe E, Miyaura C, Sakagami H, Takeda M, Konno K, Yamazaki T . Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1981; 78(8):4990-4. PMC: 320317. DOI: 10.1073/pnas.78.8.4990. View

11.

Chung I, Han G, Seshadri M, Gillard B, Yu W, Foster B . Role of vitamin D receptor in the antiproliferative effects of calcitriol in tumor-derived endothelial cells and tumor angiogenesis in vivo. Cancer Res. 2009; 69(3):967-75. PMC: 2752059. DOI: 10.1158/0008-5472.CAN-08-2307. View

12.

Xu Y, Shibata A, McNeal J, Stamey T, Feldman D, Peehl D . Vitamin D receptor start codon polymorphism (FokI) and prostate cancer progression. Cancer Epidemiol Biomarkers Prev. 2003; 12(1):23-7. View

13.

Tuohimaa P, Lyakhovich A, Aksenov N, Pennanen P, Syvala H, Lou Y . Vitamin D and prostate cancer. J Steroid Biochem Mol Biol. 2001; 76(1-5):125-34. DOI: 10.1016/s0960-0760(00)00141-2. View

14.

Rohan J, Weigel N . 1Alpha,25-dihydroxyvitamin D3 reduces c-Myc expression, inhibiting proliferation and causing G1 accumulation in C4-2 prostate cancer cells. Endocrinology. 2009; 150(5):2046-54. PMC: 2671895. DOI: 10.1210/en.2008-1395. View

15.

Barroso E, Fernandez L, Milne R, Pita G, Sendagorta E, Floristan U . Genetic analysis of the vitamin D receptor gene in two epithelial cancers: melanoma and breast cancer case-control studies. BMC Cancer. 2008; 8:385. PMC: 2639605. DOI: 10.1186/1471-2407-8-385. View

16.

Haussler M, Jurutka P, Mizwicki M, Norman A . Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)₂vitamin D₃: genomic and non-genomic mechanisms. Best Pract Res Clin Endocrinol Metab. 2011; 25(4):543-59. DOI: 10.1016/j.beem.2011.05.010. View

17.

Nemere I, Garbi N, Hammerling G, Hintze K . Role of the 1,25D3-MARRS receptor in the 1,25(OH)2D3-stimulated uptake of calcium and phosphate in intestinal cells. Steroids. 2012; 77(10):897-902. DOI: 10.1016/j.steroids.2012.04.002. View

18.

Koli K, Keski-Oja J . 1alpha,25-dihydroxyvitamin D3 and its analogues down-regulate cell invasion-associated proteases in cultured malignant cells. Cell Growth Differ. 2000; 11(4):221-9. View

19.

Matthews D, LaPorta E, Zinser G, Narvaez C, Welsh J . Genomic vitamin D signaling in breast cancer: Insights from animal models and human cells. J Steroid Biochem Mol Biol. 2010; 121(1-2):362-7. PMC: 2906670. DOI: 10.1016/j.jsbmb.2010.03.061. View

20.

Mehta R, Peng X, Alimirah F, Murillo G, Mehta R . Vitamin D and breast cancer: emerging concepts. Cancer Lett. 2012; 334(1):95-100. DOI: 10.1016/j.canlet.2012.10.034. View