Lung cancerHow does vitamin D work?

A number of mechanisms have been identified by which vitamin D reduces the risk of cancer. These include effects such as regulation of cell growth, differentiation, apoptosis and a wide range of cellular mechanisms central to the development of cancer12, regulation of calcium absorption and metabolism34, 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. E-cadherin plays a role in lung cancer7. Consistent with this theory, a murine model has demonstrated that 25(OH)D3 inhibited pulmonary metastases of the Lewis lung carcinoma8.

The vitamin D binding protein (VDPP) transports vitamin D in the body, and plays an important role in reducing lung diseases9. “VDBP is a serum protein which has immunomodulatory functions relevant in the lung, predominantly relating to macrophage activation and neutrophil chemotaxis. Variations within its gene are also associated with airways disease, implying a role for the protein product in pathogenesis.”9. Variations of the gene controlling VDBP are likely to affect the effect of VDPP on lung cancer risk 9.

Genetic variations in vitamin D receptors (VDRs) have also been found to affect risk of lung cancer survival:

There were 294 patients and 233 deaths, with median follow-up of 42 months. We found no difference in survival by circulating vitamin D level. The C/C genotype of the FokI polymorphism was associated with improved survival: median survival for C/C was 21.4 months, for C/T was 12.1 months, and for T/T was 15.6 months (log-rank P = 0.005). There were no significant effects on survival by the Cdx-2 or BsMI polymorphism. However, having increasing numbers of protective alleles was associated with improved survival (AHR for two or more vs. zero to one protective alleles, 0.57; 95% CI, 0.41 to 0.79; P = 0.0008). On haplotype analysis, the G-T-C (Cdx-2-FokI-BsmI) haplotype was associated with worse survival compared with the most common haplotype of G-C-T (AHR, 1.61; 95% CI, 1.21 to 2.14; P = 0.001)10.

More recently:

High nuclear VDR expression was associated with improved OS after adjusting for age, gender, stage, smoking status, and histology (adjusted hazard ratio, 0.36; 95% CI, 0.17-0.79). There was no association between cytoplasmic VDR expression and OS. Our results suggest that nuclear VDR status may be a prognostic marker in NSCLC11.

A study with mice demonstrated that 25(OH)D3 inhibited pulmonary metastases of the Lewis lung carcinoma8.

Page last edited: 18 July 2011

References

  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. 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.
  3. Mahabir, S. Forman, M. R. Dong, Y. Q. Park, Y. Hollenbeck, A. Schatzkin, A. Mineral intake and lung cancer risk in the NIH-American Association of Retired Persons Diet and Health study. Cancer Epidemiol Biomarkers Prev. 2010 Aug; 19 (8): 1976-83.
  4. Peterlik, M. Grant, W. B. Cross, H. S. Calcium, vitamin D and cancer. Anticancer Res. 2009 Sep; 29 (9): 3687-98.
  5. 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.
  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. Wang, G. Y. Lu, C. Q. Zhang, R. M. Hu, X. H. Luo, Z. W. The E-cadherin gene polymorphism 160C->A and cancer risk: A HuGE review and meta-analysis of 26 case-control studies. Am J Epidemiol. 2008 Jan 1; 167 (1): 7-14.
  8. Sato, T. Takusagawa, K. Asoo, N. Konno, K. Antitumor effect of 1 alpha-hydroxyvitamin D3. Tohoku J Exp Med. 1982 Dec; 138 (4): 445-6.
  9. Chishimba, L. Thickett, D. R. Stockley, R. A. Wood, A. M. The vitamin D axis in the lung: a key role for vitamin D-binding protein. Thorax. 2010 May; 65 (5): 456-62.
  10. Heist, R. S. Zhou, W. Wang, Z. Liu, G. Neuberg, D. Su, L. Asomaning, K. Hollis, B. W. Lynch, T. J. Wain, J. C. Giovannucci, E. Christiani, D. C. Circulating 25-Hydroxyvitamin D, VDR Polymorphisms, and Survival in Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2008 Oct 20;
  11. Srinivasan, M. Parwani, A. V. Hershberger, P. A. Lenzner, D. E. Weissfeld, J. L. Nuclear Vitamin D receptor expression is associated with improved survival in non-small cell lung cancer. J Steroid Biochem Mol Biol. 2010 Oct 16;