Vitamin D3 supplementation may improve relapse-free survival (RFS) in certain patients with gastrointestinal tract cancers, according to research published in JAMA Network Open.

An RFS benefit with vitamin D3 was seen among patients who were p53-immunoreactive, defined as those with anti-p53 antibodies in serum and p53 protein in more than 99% of cancer cells. The researchers observed no benefit from vitamin D3 supplementation among patients who were not p53-immunoreactive.

For this analysis, the researchers examined data from 392 patients with stage I-III gastrointestinal tract cancers from the AMATERASU trial. The patients had colorectal cancer (n=183), gastric cancer (n=170), esophageal cancer (n=37), and small bowel cancer (n=2). A total of 142 patients had detectable anti-p53 antibodies in serum, and 80 patients were in the p53-immunoreactive subgroup.

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The patients were randomly assigned to receive 2000 IU/day of vitamin D3 (n=241) or a placebo (n=151) after curative surgery.

The researchers found no significant differences in RFS between the vitamin D3 and placebo groups among patients with or without detectable anti-p53 antibodies. However, patients in the p53-immunoreactive subgroup had a significantly higher RFS rate with vitamin D3 supplementation.

In patients with detectable anti-p53 antibodies, the 5-year RFS rate was 77.2% among vitamin D3 recipients and 60.0% among placebo recipients (hazard ratio [HR], 0.57; 95% CI, 0.30-1.10). In patients without detectable anti-p53 antibodies, the 5-year RFS rate was 75.9% among vitamin D3 recipients and 72.5% among placebo recipients (HR, 0.98; 95% CI, 0.56-1.69).

In the p53-immunoreactive subgroup, the 5-year RFS rate was 80.9% among vitamin D3 recipients and 30.6% among placebo recipients (HR, 0.27; 95% CI, 0.11-0.61; P =.002). In the non-p53-immunoreactive patients, the 5-year RFS rate was 74.7% and 74.1%, respectively (HR, 1.09; 95% CI, 0.65-1.84).

“[V]itamin D supplementation reduced the risk of relapse or death in the subgroup of patients with digestive tract cancer who were p53 immunoreactive,” the researchers summarized. “Findings suggest the importance of developing cancer immunotherapy targeting mutated p53 proteins.”


Kanno K, Akutsu T, Ohdaira H, Suzuki Y, Urashima, M. Effect of vitamin D supplements on relapse or death in a p53-immunoreactive subgroup with digestive tract cancer: Post hoc analysis of the AMATERASU randomized clinical trial. JAMA Netw Open. Published online August 22, 2023. doi:10.1001/jamanetworkopen.2023.28886

This article originally appeared on Cancer Therapy Advisor