Vitamin D Effect on Advanced Colorectal Cancer Varies by Receptor Genotype

By David Douglas

December 23, 2016

NEW YORK (Reuters Health) - In patients with colorectal adenomas, vitamin D3 supplementation cuts the risk of disease advance in some but boosts it in others, according to a large clinical trial.

"Our study suggests that the effect of vitamin D supplementation on colorectal adenomas may depend on individual genetic factors," Dr. Elizabeth L. Barry of the Geisel School of Medicine at Dartmouth in Lebanon, New Hampshire, told Reuters Health by email.

In a paper online December 15 in JAMA Oncology, Dr. Barry and colleagues note that there is some evidence that vitamin D and calcium inhibit colorectal carcinogenesis.

However, after conducting a trial of up to five years of such supplementation in more than 2,200 patients with adenomas, the team "unexpectedly" found that the risk of recurrent colorectal adenomas was not reduced.

To investigate further, the researchers concentrated on 1,702 participants who completed the trial and had genotype data for analysis. The effect of vitamin D3 supplementation on advanced adenomas (but not adenoma risk overall) significantly varied according to vitamin D receptor genotypes.

In the 436 patients with the rs7968585 AA genotype, vitamin D supplementation reduced the risk by 64% (p=0.002). This amounted to an absolute risk reduction of 9.3%.

However, in 1,251 patients with one or two G alleles, supplementation increased the risk by 41% (p=0.05), with an absolute risk increase of 3.4%.

There were no significant interactions of genotypes with calcium supplementation.

"So," concluded Dr. Barry, "until we know more about how the health effects of vitamin D are modified by genetic factors, physicians should be cautious about prescribing vitamin D supplementation for hypothetical benefits like cancer prevention."

Medical oncologist Dr. Kimmie Ng, who was not involved in the study, told Reuters Health by email, "The finding of a differential effect of vitamin D supplementation on risk of recurrent adenoma according to the genotype of the vitamin D receptor is interesting and consistent with previous reports, and supports the biologic plausibility that vitamin D plays a role in colorectal cancer pathogenesis."

Dr. Ng, of the Dana-Farber Cancer Institute in Boston, added, "Some caveats about the study include the lack of a comprehensive look at germline variability, and the fact that colorectal cancer was not the endpoint."

"Further work needs to be done to understand the complex genetic and metabolic mechanisms underlying these findings, in order to better understand the potential role of vitamin D in colorectal cancer chemoprevention and treatment," she said.


JAMA Oncol 2016.