MelanomaHow does vitamin D work?

Much of the action of vitamin D occurs through vitamin D receptors (VDRs).The hormonal version of vitamin D, 1,25-dihydroxyvitamin D, acts as the key that activates the VDR, which then controls the expression of up to 2000 genes, upregulating about two thirds, downregulating about one third.

VDRs are present in different varieties or alleles. If it is found that different alleles are related to disease risk, then that is reasonably good evidence that vitamin D affects the disease outcome.

Two meta-analyses of VDR alleles and risk of melanoma found that some alleles increased or decreased risk of melanoma by 20-30%1 2.

A number of other mechanisms have been identified by which vitamin D reduces the risk of cancer, including regulation of cell growth, differentiation, apoptosis and a wide range of cellular mechanisms central to the development of cancer3 4, and reduced risk of angiogenesis and metastasis5.

A hypothesis regarding the role of vitamin D in reducing risk of cancer incidence and progression was recently proposed. It has seven phases: disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition (abbreviated DINOMIT)6.

This mechanism notes that vitamin D is a necessary co-factor for the expression of proteins that hold cells together (e.g., E-cadherin) and that mediate intercellular communication, both of which are important for restraining tissue growth and could function not only in cancer initiation, but in the control of metastasis. This hypothesis has been supported for melanoma7.

Page last edited: 18 July 2011


  1. Mocellin, S. Nitti, D. Vitamin D receptor polymorphisms and the risk of cutaneous melanoma: a systematic review and meta-analysis. Cancer. 2008 Nov 1; 113 (9): 2398-407.
  2. Randerson-Moor, J. A. Taylor, J. C. Elliott, F. Chang, Y. M. Beswick, S. Kukalizch, K. Affleck, P. Leake, S. Haynes, S. Karpavicius, B. Marsden, J. Gerry, E. Bale, L. Bertram, C. Field, H. Barth, J. H. Silva Idos, S. Swerdlow, A. Kanetsky, P. A. Barrett, J. H. Bishop, D. T. Bishop, J. A. Vitamin D receptor gene polymorphisms, serum 25-hydroxyvitamin D levels, and melanoma: UK case-control comparisons and a meta-analysis of published VDR data. Eur J Cancer. 2009 Dec; 45 (18): 3271-81.
  3. 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.
  4. Rheem, D. S. Baylink, D. J. Olafsson, S. Jackson, C. S. Walter, M. H. Prevention of colorectal cancer with vitamin D. Scand J Gastroenterol. 2010 Aug; 45 (7-8): 775-84.
  5. Krishnan, A.V. et al. The role of vitamin D in cancer prevention and treatment. Endocrinol Metab Clin North Am. 2010 Jun; 39 (2): 401-18.
  6. 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.
  7. Kreizenbeck, G. M. Berger, A. J. Subtil, A. Rimm, D. L. Gould Rothberg, B. E. Prognostic significance of cadherin-based adhesion molecules in cutaneous malignant melanoma. Cancer Epidemiol Biomarkers Prev. 2008 Apr; 17 (4): 949-58.