Let the Sun Shine: Vitamin D Appears Protective in CRC

Alok A. Khorana, MD


July 14, 2014

Plasma Vitamin D Concentration Influences Survival Outcome After a Diagnosis of Colorectal Cancer

Zgaga L, Theodoratou E, Farrington SM, et al.
J Clin Oncol. 2014 July 7. [Epub ahead of print]

Study Summary

The investigators prospectively studied 1598 patients with stage I-III colon or rectal cancers after resection. After plasma samples were obtained postoperatively, they were tested for an association between survival and 25-hydroxyvitamin D (25-OHD), vitamin D receptor (VDR) genotype/haplotype, and interactions.

At the time of testing, nearly half of the patients had low levels of vitamin D. The investigators found strong associations between plasma 25-OHD concentration and colorectal cancer-specific mortality (P = .008) and all-cause mortality (P = .003). Adjusted hazards ratios were 0.68 (95% CI, 0.50 to 0.90) and 0.70 (95% CI, 0.55 to 0.89), respectively (highest vs lowest 25-OHD tertile), particularly in stage II disease (hazard ratio, 0.44; P = .004 for CRC-specific mortality). The study also found interactions between 25-OHD level and specific VDR genotypes, suggesting a causal relationship between vitamin D and survival.


Vitamin D has been linked epidemiologically with the development of several malignancies, including colorectal cancer. This study, conducted prospectively in a large sample size of patients with resected colorectal cancer, clearly demonstrates that many patients are deficient in vitamin D, and that low levels are predictive of poor outcomes.

The high prevalence of deficiency can be attributed to the Scottish study population and northern latitudes, where sun exposure may be reduced. This limited the study's ability to gauge the effect of higher levels of vitamin D. However, the gene/environment interaction for VDR genotype suggests causality, namely that vitamin D is protective in colorectal cancer. Together, these findings suggest that low plasma levels of vitamin D may be a biomarker of poor outcomes and that vitamin D replacement therapy may benefit patients, although this remains to be proven.


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