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

• Published in: The FEBS journal 2024-06, Vol.291 (12), p.2485-2518
• Main Authors: Pereira, Fábio, Fernández-Barral, Asunción, Larriba, María Jesús, Barbáchano, Antonio, González-Sancho, José Manuel
• Format: Article
• Language: English
• Subjects: Animals; Calciferol; Calcitriol; Cancer; Clinical trials; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Dietary supplements; Endocrine system; Endocrine System - metabolism; Epidemiology; Humans; Metabolites; Molecular modelling; Receptors, Calcitriol - genetics; Receptors, Calcitriol - metabolism; Stromal cells; Tumors; Vitamin D; Vitamin D - metabolism; Vitamin D Deficiency - complications; Vitamin D Deficiency - genetics; Vitamin D Deficiency - metabolism; Vitamin D3; Vitamin deficiency
• ISSN: 1742-464X; 1742-4658; 1742-4658
• DOI: 10.1111/febs.16955

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 D [1,25(OH) D ], 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) D 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) D 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 D supplementation conducted in both healthy individuals and CRC patients.