Vitamin D Levels Linked to Survival in Colorectal Cancer

Some suggestion of causality between vitamin D and outcomes was seen in the study.

Colorectal cancer (CRC) patients with higher levels of plasma vitamin D have better survival outcomes, according to a new prospective study. Some suggestion of causality between vitamin D and outcomes was seen, though as with many vitamin D studies, the effect of supplementation remains to be seen.

“Establishing a causal relationship between CRC incidence and vitamin D deficiency is challenging because environmental risk factors associated with CRC may also be associated with vitamin D deficiency,” wrote study authors led by Malcolm G. Dunlop, MD, of the University of Edinburgh in Scotland, in the Journal of Clinical Oncology. There is also the possibility that the presence of CRC and the associated treatments could lower levels of vitamin D.

In the new study, the researchers studied 1,598 patients with stage I to III CRC, and measured plasma levels of 25-hydroxyvitamin D (25-OHD) as well as looking for variation in the vitamin D receptor (VDR) gene locus. They found some very strong correlations.

After 12,323 person-years of follow-up, higher postoperative 25-OHD levels were significantly associated with lower CRC-specific (P = .008) and all-cause (P = .003) mortality. Patients in the highest tertile of plasma 25-OHD levels had an adjusted hazard ratio (HR) for CRC-specific mortality vs the lowest tertile of 0.68 (95% CI, 0.50-0.90; P = .008). For all-cause mortality, that HR was 0.70 (95% CI, 0.55-0.89; P = .0034). The effect was strongest in patients with stage II disease.

Though there was no association between survival and VDR single nucleotide polymorphisms, the authors noted there was evidence for gene-environment interaction effects on CRC-specific mortality between vitamin D levels and certain genetic characteristics.

This combination of findings, according to the authors, suggests that “there is now a compelling case for appropriately designed and adequately powered randomized clinical trials aimed at testing whether actively supplementing the diet of patients recently diagnosed with CRC with vitamin D can have a favorable impact on survival.”

Studies on the effects of circulating levels of vitamin D, as well as on potential effects of supplementation in a number of cancers, have yielded confusing and often contradictory results to date. The authors of the new work suggest that this was the first time postoperative vitamin D levels were prospectively measured along with gene-environment interactions, which may make it more believable than some. And as with many studies, it confirmed that huge numbers of people are vitamin D deficient according to current understanding: in this cohort, 49.7% of patients were deficient, with a 25-OHD level below 10 ng/ml, and another 26.8% were at high risk of deficiency between 10 ng/ml and 16 ng/ml.