Endocrine Abstracts

Introduction: In addition to its role in phosphocalcic metabolism, the vitamin D (vitD) seems to have anti-tumor effects, particularly in colorectal cancer (CRC). The active metabolite of vitD [1,25(OH)₂D₃], converted by the enzyme CYP27B1, inhibits proliferation and promotes differentiation of CRC cells which express vitamin D receptor (VDR) via the regulation of a high number of genes. The vitD metabolism seems also to regulate inflammatory processes involved in CRC development and progression, including the CD4⁺ T cells differentiation and the cytokines production. This study aimed to investigate VitD related parameters and Th17-related parameters in CRC patients in comparison with controls.

Patients and Methods: This is a case-control study including 43 untreated CRC patients and 86 healthy controls. The expression levels of VDR, CYP27B1 and interleukin 23 receptor (IL-23R) genes in peripheral blood mononuclear cells (PBMC) were studied using a quantitative PCR (qPCR). The measurement of circulating levels of VitD (25(OH)D) and IL-17A was performed using ELISA kits.

Results: The mean level of circulating 25(OH)D was significantly lower in CRC patients in comparison with controls (13.77±7.93 vs 21.07±8.79; P=0.002, respectively). A statistically significant association was observed between VitD deficiency (25(OH)D < 20 ng/ml) and risk of CRC (OR =6.42; IC 95% =2.64 et 15.61; P<0.001). In contrary, the mean levels of VDR and CYP27B1 gene expression were significantly higher in patients than in controls (P=0.002; P=0.047, respectively). Regarding Th17 axis, the mean level of circulating IL-17A was significantly higher in patients than in controls (P=0.009). The mean level of IL-23R gene expression was higher in patients than in controls (P=0.1). The levels of 25(OH)D were inversely correlated with the circulating levels of IL-17A (r=-0.33 ;P=0.03). Furthermore, the circulating levels of IL17A were positively correlated with the gene expression levels of VDR and CYP27B1 (r=0.33; P=0.035 and r=0.39; P=0.012, respectively).

Conclusion: The vitD, by binding to its receptor (VDR), seems to regulate the expression of a high number of genes involved in CRC cell proliferation as well as T helper cell differentiation. Further clinical studies are required to confirm the close interplay between vitD, anti-tumor immunity, and CRC, suggesting a possible role of vitD as a potential agent in CRC prevention and therapy.