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Higher Plasma Vitamin D Concentration Associated With Reduced Cancer-Specific and All-Cause Mortality After Diagnosis of Colorectal Cancer

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Key Points

  • Patients with the highest 25-OHD levels had significantly reduced colorectal cancer–specific and all-cause mortality.
  • Significant interactions between 25-OHD level and vitamin D receptor genotype/haplotype for colorectal cancer–specific and all-cause mortality were observed.

In a Scottish study reported in Journal of Clinical Oncology, Zgaga et al found strong associations between plasma levels of 25-hydroxyvitamin D (25-OHD) after a diagnosis of colorectal cancer and colorectal cancer–specific and all-cause mortality. Significant interactions of vitamin D receptor genotype/haplotype and 25-OHD levels were also observed for colorectal cancer–specific and all-cause mortality.

Study Details

The study involved 1,598 Scottish patients with stage I to III colorectal cancer. Blood samples for 25-OHD measurement were taken postoperatively. At the time of sampling, 49.7% of patients had vitamin D deficiency (25-OHD < 10 ng/mL) and 26.8% were at high risk of deficiency (10–16 ng/mL). Multivariate analysis used May-adjusted 25-OHD levels and adjusted for tumor site, surgery, time between definitive treatment and sampling, season of blood collection, body mass index, and level of physical activity.

Effect on Survival

On multivariate analysis among all patients, compared with patients in the lowest 25-OHD tertile (< 7.25 ng/mL), those in the middle tertile (7.25–13.25 ng/mL) had a borderline significant reduction in all-cause mortality (hazard ratio [HR] = 0.81, P = .056) and those in the highest tertile (> 13.25 ng/mL) had a significant reduction in colorectal cancer mortality (HR = 0.68, P = .008) and all-cause mortality (HR = 0.70, P = .0034). On multivariate analysis of colorectal cancer mortality according to disease stage, patients with stage II disease in the highest tertile had significantly reduced risk (HR = 0.44, P = .004).

The effect of higher 25-OHD levels was stronger in patients not receiving chemotherapy (disease stage II and III) than in those receiving chemotherapy (HR = 0.42, P = .008, for lowest vs highest tertile), with the effect again being greatest in patients with stage II disease (HR = 0.34, 95% confidence interval = 0.14–0.81)

Genotype Interactions

There were no significant associations between survival and vitamin D receptor single nucleotide polymorphisms or haplotype doses. However, significant protective gene-environment interactions were found between 25-OHD concentration and rs11568820 genotype for colorectal cancer–specific (P = .008) and all-cause mortality (P = .022), number of protective alleles for colorectal cancer–specific (P = .004) and all-cause mortality (P = .018), and GAGC haplotype at the vitamin D receptor locus for all-cause mortality (P = .008).

The investigators concluded, “In patients with stage I to III [colorectal cancer], postoperative plasma vitamin D is associated with clinically important differences in survival outcome, higher levels being associated with better outcome. We observed interactions between 25-OHD level and [vitamin D receptor] genotype, suggesting a causal relationship between vitamin D and survival. The influence of vitamin D supplementation on [colorectal cancer] outcome will require further investigation.”

Malcolm G. Dunlop, MD, of University of Edinburgh, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by Cancer Research UK. The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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