Serum Vitamin D Metabolites in Colorectal Cancer Patients Receiving Cholecalciferol Supplementation: Correlation with Polymorphisms in the Vitamin D Genes

Cholecalciferol (D₃) supplementation results in variable increases in serum 25(OH)D₃ levels, however, the influence of genetic polymorphisms on these variable responses is unclear. We measured serum 25(OH)D₃, 24,25(OH)₂D_3, 1,25(OH)₂D₃ and VDBP levels in 50 colorectal cancer (CRC) patients before and during 2,000 IU daily oral D₃ supplementation for six months and in 263 archived CRC serum samples. Serum PTH levels and PBMC 24-OHase activity were also measured during D₃ supplementation. TagSNPs in CYP2R1, CYP27A1, CYP27B1, CYP24A1, VDR, and GC genes were genotyped in all patients, and the association between these SNPs and serum vitamin D₃ metabolites levels before and after D₃ supplementation was analyzed. The mean baseline serum 25(OH)D₃ level was less than 32 ng/mL in 65 % of the 313 CRC patients. In the 50 patients receiving D₃ supplementation, serum levels of 25(OH)D₃ increased (p?=?0.008), PTH decreased (p?=?0.036) and 24,25(OH)₂D₃, 1,25(OH)₂D₃, VDBP levels and PBMC 24-OHase activity were unchanged. GC SNP rs222016 was associated with high 25(OH)D₃ and 1,25(OH)₂D₃ levels at baseline while rs4588 and rs2282679 were associated with lower 25(OH)D₃ and 1,25(OH)₂D₃ levels both before and after D₃ supplementation. CYP2R1 rs12794714 and rs10500804 SNPs were significantly associated with low 25(OH)D₃ levels after supplementation but not with baseline 25(OH)D₃. Our results show that D₃ supplementation increased 25(OH)D₃ levels in all patients. GC rs4588 and rs2283679 SNPs were associated with increased risk of vitamin D₃ insufficiency and suboptimal increase in 25(OH)D₃ levels after D₃ supplementation. Individuals with these genotypes may require higher D₃ supplementation doses to achieve vitamin D₃ sufficiency.