title: Serum vitamin D metabolites in colorectal cancer patients receiving cholecalciferol supplementation: correlation with polymorphisms in the vitamin D genes.
abstract: Cholecalciferol (D(3)) supplementation results in variable increases in serum 25(OH)D(3) levels, however, the influence of genetic polymorphisms on these variable responses is unclear. We measured serum 25(OH)D(3), 24,25(OH)(2)D(3), 1,25(OH)2D(3) and VDBP levels in 50 colorectal cancer (CRC) patients before and during 2,000 IU daily oral D(3) supplementation for six months and in 263 archived CRC serum samples. Serum PTH levels and PBMC 24-OHase activity were also measured during D(3) 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 D(3) metabolites levels before and after D(3) supplementation was analyzed. The mean baseline serum 25(OH)D(3) level was less than 32 ng/mL in 65 % of the 313 CRC patients. In the 50 patients receiving D(3) supplementation, serum levels of 25(OH)D(3) increased (p = 0.008), PTH decreased (p = 0.036) and 24,25(OH)(2)D(3), 1,25(OH)(2)D(3), VDBP levels and PBMC 24-OHase activity were unchanged. GC SNP rs222016 was associated with high 25(OH)D(3) and 1,25(OH)(2)D(3) levels at baseline while rs4588 and rs2282679 were associated with lower 25(OH)D(3) and 1,25(OH)(2)D(3) levels both before and after D(3) supplementation. CYP2R1 rs12794714 and rs10500804 SNPs were significantly associated with low 25(OH)D(3) levels after supplementation but not with baseline 25(OH)D(3). Our results show that D(3) supplementation increased 25(OH)D(3) levels in all patients. GC rs4588 and rs2283679 SNPs were associated with increased risk of vitamin D(3) insufficiency and suboptimal increase in 25(OH)D(3) levels after D(3) supplementation. Individuals with these genotypes may require higher D(3) supplementation doses to achieve vitamin D(3) sufficiency.
authors: Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. Josephia.muindi@roswellpark.org
authors: Josephia R
authors: JR
authors: Muindi
authors: Araba A
authors: AA
authors: Adjei
authors: Zengru R
authors: ZR
authors: Wu
authors: Isabel
authors: I
authors: Olson
authors: Huayi
authors: H
authors: Huang
authors: Adrienne
authors: A
authors: Groman
authors: Lili
authors: L
authors: Tian
authors: Prashant K
authors: PK
authors: Singh
authors: Lara E
authors: LE
authors: Sucheston
authors: Candace S
authors: CS
authors: Johnson
authors: Donald L
authors: DL
authors: Trump
authors: Marwan G
authors: MG
authors: Fakih
mesh_terms: D000328:Adult; D000368:Aged; D002762:Cholecalciferol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015179:Colorectal Neoplasms / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D019587:Dietary Supplements; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics; D017422:Sequence Analysis, DNA; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D014809:Vitamin D-Binding Protein / Q000097:blood / Q000235:genetics*; D065668:Vitamin D3 24-Hydroxylase; D014815:Vitamins / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D014809:Vitamin D-Binding Protein; D014815:Vitamins; D002762:Cholecalciferol; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase