Renal cancerHow does vitamin D work?

Vitamin D may reduce the risk of cancer by regulating cell growth, differentiation, apoptosis and though effects on gene expression

A number of mechanisms have been identified by which vitamin D reduces the risk of renal cancer.  These include effects such as regulation of cell growth, differentiation, apoptosis and a wide range of cellular mechanisms central to the development of cancer1, increased absorption of calcium2, reduced angiogenesis around tumors3 and reduced metastasis4, and prevention of epithelial cell disjunction5.

Calcium intake has been found correlated with reduced risk of renal cancer6

Much of the beneficial effect of vitamin D in reducing the risk of renal and other cancers is through the action of the active metabolite of vitamin D, 1,25-hydroxyvitamin D, on vitamin D receptors, which control expression of hundreds of genes7869.

Individuals with Von Hippel-Lindau syndrome have a high risk of developing kidney cancer, because they inherit a mutation in the VHL protein that causes the protein’s normal function to be lost or altered. VHL is a tumor suppressor gene that inhibits production of Hypoxia-inducible factor (HIF)10. HIF is essential for renal cancer formation and progression, and activated vitamin D has in vitro been shown to decrease the expression of HIF and inhibit angiogenesis through  HIF-dependent upregulation of VEGF11. This anti-neoplastic effect is also found in vivo studies, where induced tumors were larger and had higher levels of HIF in mice lacking VDR (VDR knockout mice) compared to controls12. Furthermore, 1,25(OH)2D3  treatment of mice with kidney cancer increased survival, and inhibited tumour growth, angiogenesis and metastasis313.

Page last edited: 01 July 2011


  1. Ingraham, B. A. Bragdon, B. Nohe, A. Molecular basis of the potential of vitamin D to prevent cancer. Curr Med Res Opin. 2008 Jan; 24 (1): 139-49.
  2. Peterlik, M, Grant , W. B, Cross, H.S. Calcium, vitamin D and cancer. Anticancer Res. 2009 Sept; 29 (9): 3687-98.
  3. Fujioka, T. Hasegawa, M. Ishikura, K. Matsushita, Y. Sato, M. Tanji, S. Inhibition of tumor growth and angiogenesis by vitamin D3 agents in murine renal cell carcinoma. J Urol. 1998 Jul; 160 (1): 247-51.
  4. Krishnan, A. V. Trump, D. L. Johnson, C. S. Feldman, D. The role of vitamin D in cancer prevention and treatment. Endocrinol Metab Clin North Am. 2010 Jun; 39 (2): 401-18, table of contents.
  5. Garland, C. F. Gorham, E. D. Mohr, S. B. Garland, F. C. Vitamin D for cancer prevention: global perspective. Ann Epidemiol. 2009 Jul; 19 (7): 468-83.
  6. Karami, S. Brennan, P. Navratilova, M. Mates, D. Zaridze, D. Janout, V. Kollarova, H. Bencko, V. Matveev, V. Szesznia-Dabrowska, N. Holcatova, I. Yeager, M. Chanock, S. Rothman, N. Boffetta, P. Chow, W. H. Moore, L. E. Vitamin d pathway genes, diet, and risk of renal cell carcinoma. Int J Endocrinol. 2010; 2010879362.
  7. Blomberg Jensen, M. Andersen, C. B. Nielsen, J. E. Bagi, P. Jorgensen, A. Juul, A. Leffers, H. Expression of the vitamin D receptor, 25-hydroxylases, 1alpha-hydroxylase and 24-hydroxylase in the human kidney and renal clear cell cancer. J Steroid Biochem Mol Biol. 2010 Jul; 121 (1-2): 376-82.
  8. Karami, S. Brennan, P. Rosenberg, P. S. Navratilova, M. Mates, D. Zaridze, D. Janout, V. Kollarova, H. Bencko, V. Matveev, V. Szeszenia-Dabrowska, N. Holcatova, I. Yeager, M. Chanock, S. Menashe, I. Rothman, N. Chow, W. H. Boffetta, P. Moore, L. E. Analysis of SNPs and haplotypes in vitamin D pathway genes and renal cancer risk. PLoS One. 2009; 4 (9): e7013.
  9. Obara, W. Suzuki, Y. Kato, K. Tanji, S. Konda, R. Fujioka, T. Vitamin D receptor gene polymorphisms are associated with increased risk and progression of renal cell carcinoma in a Japanese population. Int J Urol. 2007 Jun; 14 (6): 483-7.
  10. Gnarra JR, Tory K, Weng Y, Schmidt L, Wei MH, Li H, et al Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat. Genet. 1994; 7 (1): 85–90.
  11. Ben-Shoshan M, Amir S, Dang DT, Dang LH, Weisman Y, Mabjeesh NJ. 1alpha,25-dihydroxyvitamin D3 (calcitriol) inhibits hypoxia-inducible factor-1/vascular endothelial growth factor pathway in human cancer cells. Mol.Cancer Ther. 2007 Apr; 6 (4): 1433-9.
  12. Chung I, Han G, Seshadri M, Gillard BM, Yu WD, Foster BA, Trump DL, Johnson CS Role of vitamin D receptor in the antiproliferative effects of calcitriol in tumour-derived endothelial cells and tumour angiogenesis in vivo. Cancer Res. 2009; 69 (3): 967–975.
  13. Yacobi R, Koren R, Liberman UA, Rotem C, Wasserman L, Ravid A 1,25-dihydroxyvitamin D3 increases the sensitivity of human renal carcinoma cells to tumour necrosis factor alpha but not to interferon alpha or lymphokineactivated killer cells. J. Endocrinol. 1996; 149 (2): 327–333.