From molecular basis to clinical insights: a challenging future for the vitamin D endocrine system in colorectal cancer
Fábio Pereira, Asunción Fernández‐Barral, María Jesús Larriba, Antonio Barbáchano, José Manuel González‐Sancho
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 D 3 [1,25(OH) 2 D 3 ], 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) 2 D 3 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) 2 D 3 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 3 supplementation conducted in both healthy individuals and CRC patients.