{
  "abstract": "Background/Objectives: Vitamin D supplementation effects may vary according to receptor genotype and tumor receptor abundance. We examined whether treatment effects differed according to FokI genotype and tumor nuclear vitamin D receptor (VDR) expression after surgery for digestive tract cancer. Methods: This exploratory post hoc analysis used data from the double-blind AMATERASU randomized trial (UMIN000001977), which assigned 417 patients with resected stage I–III digestive tract cancers to vitamin D3 (2000 IU/day) or placebo. FokI genotype was determined by sequencing and nuclear VDR expression by immunohistochemistry. Unadjusted Cox analyses were supplemented by pooled treatment-by-subgroup interaction models adjusted for age, sex, and pathological stage, with baseline hazards stratified by tumor site. Results: The joint analysis included 359 patients (213 vitamin D; 146 placebo). VDR expression varied across tumor sites. Among patients with the FokI CC genotype and VDR expression in quintiles 2–5 (n = 110), the unadjusted treatment hazard ratio (HR) for relapse or death was 0.30 (95% confidence interval [CI], 0.12–0.73), compared with 1.02 (95% CI, 0.61–1.71) in the complementary subgroup (n = 249; nominal interaction p = 0.02). After adjustment, the HR in the CC/VDR Q2–5 subgroup was 0.44 (95% CI, 0.18–1.10; interaction p = 0.211). For all-cause mortality, the adjusted HR was 0.46 (95% CI, 0.14–1.51; interaction p = 0.135). Conclusions: The unadjusted exploratory findings were attenuated after accounting for clinicopathological factors. Differential supplementation benefit according to the joint classification was not established. Independent validation is required before clinical use.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Molecular Epidemiology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-Ku, Tokyo 105-8461, Japan",
    "Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-Ku, Tokyo 105-8461, Japan",
    "Department of Surgery, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara 329-2763, Tochigi, Japan"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Tadashi Matsushima",
      "orcid": "0009-0006-3677-0439"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Akitaka Sasaki"
    },
    {
      "affs": [
        0
      ],
      "name": "Taisuke Akutsu",
      "orcid": "0000-0003-3649-4519"
    },
    {
      "affs": [
        2
      ],
      "name": "Hironori Ohdaira"
    },
    {
      "affs": [
        2
      ],
      "name": "Yutaka Suzuki"
    },
    {
      "affs": [
        0
      ],
      "name": "Mitsuyoshi Urashima",
      "orcid": "0000-0002-7395-5831"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5nb1t0402s12j.bib",
  "cited_by": 0,
  "doi": "10.3390/cancers18213570",
  "fulltext_url": null,
  "id": "5nb1t0402s12j",
  "issns": [
    "2072-6694"
  ],
  "landing_url": "https://www.mdpi.com/2072-6694/18/21/3570",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/5nb1t0402s12j.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:21:21Z",
      "native_id": "10.3390/cancers18213570",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6694/18/21/3570"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2072-6694",
      "subfield": "oncology"
    }
  ],
  "title": "Vitamin D Receptor Genotype, Tumor Expression, and Outcomes After Vitamin D Supplementation in Digestive Tract Cancer: An Exploratory Post Hoc Analysis of the AMATERASU Trial",
  "title_text": "Vitamin D Receptor Genotype, Tumor Expression, and Outcomes After Vitamin D Supplementation in Digestive Tract Cancer: An Exploratory Post Hoc Analysis of the AMATERASU Trial",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T00:23:01Z",
  "url": "https://research.draconitic.com/paper/5nb1t0402s12j",
  "venue": "Cancers",
  "versions": []
}