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 cancer1 2, regulation of calcium absorption and metabolism3 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. 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


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