Serum vitamin D concentration, vitamin D‐related polymorphisms, and colorectal cancer risk

Serum 25‐hydroxyvitamin D (25(OH)D) has been demonstrated to be associated with risk of colorectal cancer (CRC). However, it remains unclear whether this association was modified by vitamin D‐related polymorphisms. We evaluated association of serum 25(OH)D concentration with CRC risk among 403 170 participants from UK Biobank Project. Two variants of vitamin D binding protein (VDBP), rs4588 and rs7041, were included to estimate the binding affinity of 25(OH)D to VDBP, and three variants of vitamin D receptor (VDR), rs11568820, rs2228570 and rs1544410, which may influence VDR activity, were also investigated. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During 4 957 677 person‐years of follow‐up, 5053 incident CRC cases were documented. Higher serum 25(OH)D concentrations were significantly associated with lower CRC incidence in a dose‐response manner, with HR (95% CIs) being 0.94 (0.91‐0.97) per 1 SD increment of serum 25(OH)D level (Ptrend