Vitamin D and colon cancer

Abstract

<jats:p>The most active vitamin D metabolite, 1α,25-dihydroxyvitamin D<jats:sub>3</jats:sub>(1,25(OH)<jats:sub>2</jats:sub>D<jats:sub>3</jats:sub>), is a pleiotropic hormone with wide regulatory actions. Classically, vitamin D deficiency was known to alter calcium and phosphate metabolism and bone biology. In addition, recent epidemiological and experimental studies support the association of vitamin D deficiency with a large variety of human diseases, and particularly with the high risk of colorectal cancer. By regulating the expression of many genes via several mechanisms, 1,25(OH)<jats:sub>2</jats:sub>D<jats:sub>3</jats:sub>induces differentiation, controls the detoxification metabolism and cell phenotype, sensitises cells to apoptosis and inhibits the proliferation of cultured human colon carcinoma cells. Consistently, 1,25(OH)<jats:sub>2</jats:sub>D<jats:sub>3</jats:sub>and several of its analogues decrease intestinal tumourigenesis in animal models. Molecular, genetic and clinical data in humans are scarce but they suggest that vitamin D is protective against colon cancer. Clearly, the available evidence warrants new, well-designed, large-scale trials to clarify the role of vitamin D in the prevention and/or therapy of this important neoplasia.</jats:p>

Association between Circulating Vitamin D, the Taq1 Vitamin D Receptor Gene Polymorphism and Colorectal Cancer Risk among Jordanians

“…Many studies showed the anti cancer role of vitamin D in colorectal cancer (Zinser et al, 2003;Bouillon et al, 2008;Pereira et al, 2012;Zheng et al, 2012;Rasool et al, 2013;Yu et al, 2014), which is mediated by binding of the active form 1,25(OH) 2 D to the VDR (Marcinkowska. 2001).…”

“…2001). In advanced CRC stages VDR expression decreases (Larriba and Mun˜oz., 2005;Matusiak et al, 2005;Anderson et al, 2006), and blocks the anti-cancer action of 1, 25(OH) 2 D (Pereira et al, 2012). Both 25 (OH) D and 1, 25(OH) 2 D have localized effect in colon tissue mediated by reducing cell proliferation and inducing cell differentiation (Seifert et al, 2009).…”

“…The second hydroxylation occurs in the kidney where 25(OH)D is converted to the active form 1, 25 dihydroxyvitamin D (1,25(OH) 2 D) (Holick et al, 2011). The main role of 1, 25(OH) 2 D is calcium-phosphate homeostasis (Verstuyf et al, 2010), regulation of cell cycle (Pereira et al, 2012), and nowadays it has anticancer effect especially among colon cancer (Holick etal., 2011;Welsh, 2012 (Haussler et al, 2011). VDR is a protein consists of 427 amino acids, with a molecular weight of about forty eight KDa (Bouillon et al, 2008).…”

“…When 1, 25(OH) 2 D is absent, VDR-RXR heterodimer binds to a specific sequence within its target vitamin D-responsive gene named vitamin D response elements (VDREs) (Byers et al, 2012). Also it binds to transcriptional co-repressors and silencing mediators which maintain a repressed transcriptional state (Pereira et al, 2012).…”

“…Many genetic studies evaluated the association between Taq1 VDR gene polymorphisms and colorectal cancer (Slattery et al, 2001;Peters et al, 2004;Flugge et al, 2007;YaylimEraltan et al, 2007). Results were contraversial, and the anti-cancer mechanism of vitamin D (Ashktorab et al, 2011;Gunduz et al, 2012;Pereira et al, 2012;Vuolo et al, 2012) is unclear.…”