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 genes7 8 6 9.
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 metastasis3 13.
Page last edited: 01 July 2011
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- 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.
- 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.
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- 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.