From molecular basis to clinical insights: a challenging future for the vitamin D endocrine system in colorectal cancer

FEBS J. 2024 Jun;291(12):2485-2518. doi: 10.1111/febs.16955. Epub 2023 Sep 20.

Abstract

Colorectal cancer (CRC) is one of the most life-threatening neoplasias in terms of incidence and mortality worldwide. Vitamin D deficiency has been associated with an increased risk of CRC. 1α,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the most active vitamin D metabolite, is a pleiotropic hormone that, through its binding to a transcription factor of the nuclear receptor superfamily, is a major regulator of the human genome. 1,25(OH)2D3 acts on colon carcinoma and stromal cells and displays tumor protective actions. Here, we review the variety of molecular mechanisms underlying the effects of 1,25(OH)2D3 in CRC, which affect multiple processes that are dysregulated during tumor initiation and progression. Additionally, we discuss the epidemiological data that associate vitamin D deficiency and CRC, and the most relevant randomized controlled trials of vitamin D3 supplementation conducted in both healthy individuals and CRC patients.

Keywords: colorectal cancer; epidemiology; mechanisms of action; randomized controlled trials; vitamin D.

Publication types

  • Review

MeSH terms

  • Animals
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Endocrine System / metabolism
  • Humans
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Vitamin D Deficiency* / complications
  • Vitamin D Deficiency* / genetics
  • Vitamin D Deficiency* / metabolism
  • Vitamin D* / metabolism

Substances

  • Vitamin D
  • Receptors, Calcitriol