Abstract
Vitamin D has been shown to suppress the growth of cancer cells. Cancer cells are believed to take up bioavailable 25-hydroxyvitamin D (25[OH]D) (i.e., not bound to vitamin-D-binding protein (DBP)) more efficiently than DBP-bound 25(OH)D. Our aim was to use this bioavailable 25(OH)D, rather than total 25(OH)D, as a biomarker of vitamin D deficiency to investigate whether vitamin D supplementation improves the relapse-free survival (RFS) of patients with digestive tract cancer from the esophagus to the rectum by conducting a post hoc analysis of the AMATERASU trial (UMIN000001977). The bioavailable 25(OH)D levels were calculated via an equation using data of serum total 25(OH)D, albumin, and DBP levels, and DBP genotypes (rs7041 and rs4588). We estimated bioavailable 25(OH) levels in 355 patients. In a subgroup of patients with low bioavailable 25(OH)D levels (<median) (n = 177), 5 year RFS was 77% in the vitamin D group vs. 58% in the placebo group (hazard ratio, 0.54; 95% confidence interval, 0.31–0.95; p = 0.03), whereas no significant difference was seen in a subgroup of patients with high bioavailable 25(OH)D levels (p for interaction = 0.046). We hypothesize that vitamin D supplementation may be effective in improving RFS among digestive tract cancer patients with low bioavailable 25(OH)D levels.
Highlights
Vitamin D can be obtained from skin exposed to sunlight, diet, or supplements
It is metabolized in the liver to 25-hydroxyvitamin D (25[OH]D), and is further activated in the kidneys through
We previously conducted the AMATERASU randomized, double-blind, placebo-controlled trial of postoperative oral vitamin D3 supplementation (2000 IU/day) in 417 patients with stage I to III digestive tract cancer from the esophagus to the rectum who underwent curative surgery (UMIN000001977) [5]. In this post hoc analysis using residual serum samples and clinical data from the AMATERASU trial, we aimed to explore whether vitamin D supplementation improved survival in a subgroup of patients with lower than median levels of bioavailable 25(OH)D
Summary
Vitamin D can be obtained from skin exposed to sunlight, diet, or supplements. It is metabolized in the liver to 25-hydroxyvitamin D (25[OH]D), and is further activated in the kidneys through1α−hydroxylase to 1,25-dihydroxyvitamin D (1,25[OH]2D), which is considered to facilitate calcium absorption and improve bone health [1]. 1,25[OH]2D is metabolized by the enzyme CYP24A1, limiting calcitriol action by catabolism. It is metabolized in the liver to 25-hydroxyvitamin D (25[OH]D), and is further activated in the kidneys through. 1,25[OH]2D is released into the serum; in addition to its action on bone, it can act on the intestine and kidney to regulate calcium metabolism. CYP27B1 and CYP24A1 are found in numerous tissues throughout the body, including the skin, colon, pancreas, liver, brain, and placenta, allowing for 1,25[OH]2D synthesis and degradation [2]. In addition to this classical pathway, the 25(OH)D molecule in the serum has been hypothesized to be absorbed by cancer cells, Cancers 2020, 12, 347; doi:10.3390/cancers12020347 www.mdpi.com/journal/cancers
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