• George Ciulei, Olga Hilda Orasan, Sorina Cezara Coste, Angela Cozma, Vasile Negrean, and Lucia Maria Procopciuc.
• Department 5 Internal Medicine, 4th Medical Clinic, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
• Eur. J. Clin. Invest. 2020 Sep 1; 50 (9): e13265.

AbstractEpidemiological studies have strongly associated lower levels of vitamin D and its metabolites with an increased risk of colorectal cancer (CRC). The action of calcitriol, the active metabolite of vitamin D, is mediated by the vitamin D receptor (VDR) that is present in most tissues. In advanced CRC, VDR expression is lowered. Calcitriol has several antineoplastic effects in CRC: it promotes the G1-phase cycle arrest, lowers vascular endothelial growth factor (VEGF) synthesis and acts on tumour stromal fibroblasts to limit cell migration and angiogenesis. Hyperinsulinemia and insulin-like growth factors (IGFs) have been implicated in the pathophysiology of CRC. IGF-1 and IGFBP-3 have been the most studied components of the IGF system. Only 1% of the total serum IGF-1 is free and bioactive, and 80% of it binds to IGFBP-3. IGF-1 and its receptor IGF-1R are known to induce cell proliferation. Both IGF-1 and IGFBP-3 can favour angiogenesis by increasing the transcription of the VEGF gene. A high serum IGF-1/IGFBP-3 ratio is associated with increased risk for CRC. VDR is a transcription factor for the IGFBP-3 gene, and IGF-1 can increase calcitriol synthesis. Studies examining the effect of vitamin D treatment on serum IGF-1 and IGFBP-3 have not been in agreement since different populations, dosages and intervention periods have been used. New vitamin D treatment studies that examine CRC should take in account confounding factors such as obesity or VDR genotypes.© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

43 keywords...

hide…