Vitamin D Status, Cdx2 Genotype, and Colorectal Cancer Survival: Population-Based Patient Cohort

Abstract

According to recent evidence, the prognostic value of Vitamin D (VitD) status for colorectal cancer (CRC) patients might be confined to patients with the GG genotype of Cdx2, a functional polymorphism of the VitD receptor gene. We aimed to validate these findings in a cohort of CRC patients. Post-operative serum 25-hydroxyvitamin D concentration was determined by mass spectrometry and Cdx2 genotyping was performed from blood or buccal swabs using standard methods. Joint associations of VitD status and Cdx2 with overall survival (OS), CRC-specific survival (CSS), recurrence-free survival (RFS), and disease-free survival (DFS) were assessed using Cox regression. For patients with GG genotype, adjusted hazard ratios (95% confidence interval) for the associations of sufficient compared with deficient VitD were 0.63 (0.50–0.78), 0.68 (0.50–0.90), 0.66 (0.51–0.86), and 0.62 (0.50–0.77) for OS, CSS, RFS, and DFS, respectively. These associations were weaker and not statistically significant for the AA/AG genotype. Interaction between VitD status and genotype did not reach statistical significance. VitD deficiency is an independent predictor of poorer survival, particularly for the GG Cdx2 carriers, suggesting a potential role of VitD supplementation according to VitD status and genotype, which should be evaluated in randomised trials.

SIRT1 mediates the antagonism of Wnt/β-catenin pathway by vitamin D in colon carcinoma cells

“…However, data from supplementation studies in the human population are controversial, and confirmation of a clinically relevant anti-CRC effect of VD in well-designed prospective randomized trials is pending [5–9]. Post-hoc analyses indicate that this discrepancy may rely on the lack of patient stratification in the clinical trials, suggesting that VD intervention is effective in the deficient/insufficient VD subjects but not in VD sufficient individuals, and is also dependent on conditions such as patient body mass, ethnicity, mutational status, or genotype of VD-related genes [6,10,11]. Importantly, many mechanistic experimental studies show a wide range of antitumoral effects of VD in CRC and other neoplasia that strongly support a protective VD action [12–14].…”