Scope of Problem
The potential role of vitamin D in cancer prevention has been widely discussed in the oncology literature. Various trials have examined vitamin D status in different tumor types and suggested that deficiencies may play a role in the development of specific cancers. The recently published Institute of Medicine’s (IOM) report contains recommendations for intake of vitamin D and calcium for various age groups based on an extensive review of over 1000 studies. 1 The IOM examined the evidence linking vitamin D with skeletal and nonskeletal health outcomes and concluded that vitamin D is critical to bone health. 2 However, when reviewing outcomes for other diseases, including cancer, the evidence was considered inconsistent as to causality. 2
Previously published research has suggested that a decrease in the risk of colorectal cancer (CRC) is linked with higher plasma levels of vitamin d (25-hydroxyvitamin D3 [25(OH)D]. 3 Ng and colleagues report on a prospective trial of 515 patients with stage IV CRC who were participating in a randomized trial of chemotherapy. 3 Plasma 25 (OH)D levels were measured in all patients; vitamin D deficiency was defined as a level lower than 20 ng/mL, insufficiency as 20-29 ng/mL, and sufficiency as > 30 ng/mL. The authors examined the association between baseline levels of vitamin D and specific patient characteristics in an effort to determine the prevalence of vitamin D deficiency in patients with advanced CRC and its influence on outcomes. 3
- 50% of the 515 patients were vitamin D deficient
- 82% were vitamin D insufficient
- Plasma 25(OH)D levels were lower in black patients compared to white patients and patients of other races (median, 10.7 v 21.1 v 19.3 ng/mL, respectively, P < .001)
- Levels were lower in females compared to males, (18.3 v 21.7 ng/mL, respectively, P = .0005)
- Vitamin D levels were not significantly associated with patient age, performance status, body mass index, type of chemotherapy, geographic region, or number of metastatic sites
- Baseline levels of plasma 25(OH)D levels were not associated with patient outcome and higher levels did not correspond with improved tumor response, although statistical power for survival analyses were limited in this study
The authors concluded that vitamin D deficiency is highly prevalent in patients with stage IV CRC receiving initial chemotherapy; over 80% of patients with metastatic disease had insufficient levels of vitamin D. Female and black patients were particularly at risk. Further study is needed in this patient population.
The volume of published studies on the association between lower vitamin D levels and the presence of specific types of cancer is considerable. Data exists on potential relationships between lower vitamin D levels and breast, CRC and prostate cancer, but studies are inconclusive. Vitamin D insufficiency is pandemic in the US; possible reasons for this deficiency is the increased use of sunscreen for the prevention of skin cancer, decreased outdoor activity, and the increase in obesity for our population. A previous study demonstrated that CRC mortality is higher in US patients who live at higher latitudes; is vitamin D deficiency the reason for poorer outcomes with this common disease? 4 The lack of large, randomized trial evidence is an important factor and prevents us from making conclusions regarding the role of vitamin D. Until this evidence exists, it is difficult to make a clear association between the vitamin D deficiency and the incidence of specific cancers, including CRC. The IOM committee found that the data linking reduced cancer incidence and vitamin D sufficiency was inconsistent and inconclusive as to causality, although clear benefits regarding vitamin D and bone health are present. Although the study results reported above are intriguing, we need large, well-designed trials to definitively answer the question of vitamin D and its role in cancer.
- Institute of Medicine (IOM). Dietary Reference Intakes for Calcium and Vitamin D. 2010. Free full text available at: http://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Report%20Brief.pdf
- Manson, J.E., Mayne, S.T., & Clinton, S.K. Vitamin D and prevention of cancer – Ready for prime time? N Engl J Med 2011; Mar 23 [Epub ahead of print]. doi:10.1056/NEJMp1102022 Link to free full text at: http://www.nejm.org/doi/full/10.1056/NEJMp1102022
- Ng, K., Sargent, D.J., Goldberg, R.M. et al. Vitamin D status in patients with stage IV colorectal cancer: Findings from Intergroup trial N9741. J Clin Oncol 2011; 29 [Epub ahead of print]. doi:10.1200/JCO.2010.31.7255 Link to abstract at: http://www.ncbi.nlm.nih.gov/pubmed/21422438
- Grant, W.B. An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer 2002; 94:1867-75. doi:10.1002/cncr.10427 Link to free full text at:http://onlinelibrary.wiley.com/doi/10.1002/cncr.10427/pdf