title: Vitamin D related genes, CYP24A1 and CYP27B1, and colon cancer risk.
abstract: Genetic association studies investigating the role of vitamin D in colon cancer have primarily focused on the vitamin D receptor (VDR), with limited data available for other genes in the vitamin D pathway, including vitamin D activating enzyme 1-alpha hydroxylase (CYP27B1) and vitamin D deactivating enzyme 24-alpha hydroxylase (CYP24A1). We evaluated whether 12 tagging single nucleotide polymorphisms (SNP) in CYP24A1, identified by resequencing the gene in 32 Caucasian samples, and 1 SNP in CYP27B1 were associated with colon cancer risk. In addition, we evaluated whether these two genes modify associations between colon cancer on the one hand and total vitamin D intake and UV-weighted sun exposure on the other, as well as other variants in VDR. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the association between polymorphisms and haplotypes in CYP27B1 and CYP24A1 in a multicenter population-based case-control study of 1,600 cases and 1,949 controls. The CYP24A1 polymorphism IVS4-66T > G showed a statistically significant association with risk of colon cancer overall, particularly for proximal colon cancer. When stratified by anatomic site, we also found statistically significant associations for three CYP24A1 polymorphisms with risk of distal colon cancer (IVS4 + 1653C > T: OR for CT/TT versus CC, 0.81; 95% CI, 0.68-0.96; IVS9 + 198T > C: OR for CC versus TT, 1.33; 95% CI, 1.03-1.73; and within whites only: +4125bp 3' of STPC > G: OR for GG versus CC, 1.44; 95% CI, 1-2.05). In addition, a possible interaction between CYP27B1 and UV-weighted sun exposure with proximal colon cancer was observed. As this is the first study to evaluate these genes in relation to colon cancer, additional studies are needed to confirm these results.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Dong
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
authors.forename: Li
authors.initials: L
authors.lastname: Hsu
authors.forename: David J
authors.initials: DJ
authors.lastname: Duggan
authors.forename: Debbie S
authors.initials: DS
authors.lastname: Benitez
authors.forename: Emily
authors.initials: E
authors.lastname: White
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.forename: Fred M
authors.initials: FM
authors.lastname: Farin
authors.forename: Karen W
authors.initials: KW
authors.lastname: Makar
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.forename: Bette J
authors.initials: BJ
authors.lastname: Caan
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peters
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism; D014807:Vitamin D / Q000235:genetics* / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase
references.citation: Hum Mol Genet. 2001 Mar 15;10(6):591-7
references.pmid: 11230178
references.citation: Carcinogenesis. 2005 Sep;26(9):1581-9
references.pmid: 15905206
references.citation: J Am Diet Assoc. 1991 Sep;91(9):1104-12
references.pmid: 1918764
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Sep;13(9):1502-8
references.pmid: 15342452
references.citation: Cancer Res. 2000 Apr 15;60(8):2304-12
references.pmid: 10786699
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3568-71
references.pmid: 12824367
references.citation: Cancer Res. 1991 Oct 15;51(20):5608-13
references.pmid: 1913678
references.citation: Am J Epidemiol. 2007 May 15;165(10):1178-86
references.pmid: 17379616
references.citation: Cancer Causes Control. 1997 Jul;8(4):615-25
references.pmid: 9242478
references.citation: CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
references.pmid: 18287387
references.citation: Cancer Causes Control. 2000 May;11(5):459-66
references.pmid: 10877339
references.citation: J Natl Cancer Inst. 1985 Aug;75(2):185-91
references.pmid: 3894750
references.citation: Am J Epidemiol. 1994 Dec 1;140(11):1020-8
references.pmid: 7985650
references.citation: J Histochem Cytochem. 2004 Jul;52(7):985-9
references.pmid: 15208365
references.citation: J Biol Chem. 2005 May 27;280(21):20604-11
references.pmid: 15788398
references.citation: Cancer Causes Control. 2003 Feb;14(1):1-12
references.pmid: 12708719
references.citation: Nat Rev Cancer. 2003 Aug;3(8):601-14
references.pmid: 12894248
references.citation: Int J Epidemiol. 1998 Oct;27(5):788-93
references.pmid: 9839734
references.citation: Science. 2007 Jan 26;315(5811):466-7
references.pmid: 17185559
references.citation: Curr Opin Gastroenterol. 2006 Jan;22(1):24-9
references.pmid: 16319673
references.citation: N Engl J Med. 2006 Feb 16;354(7):684-96
references.pmid: 16481636
references.citation: Cancer Epidemiol Biomarkers Prev. 2001 Dec;10(12):1267-74
references.pmid: 11751444
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3812-4
references.pmid: 12824425
references.citation: Int J Cancer. 2002 Oct 10;101(5):403-8
references.pmid: 12216066
references.citation: Am J Hum Genet. 2000 Aug;67(2):518-22
references.pmid: 10859209
references.citation: J Biol Chem. 1992 Jan 5;267(1):83-90
references.pmid: 1730627
references.citation: Lancet. 2001 May 26;357(9269):1673-4
references.pmid: 11425375
references.citation: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W280-6
references.pmid: 15215395
references.citation: Cancer Causes Control. 2001 May;12(4):359-64
references.pmid: 11456232
references.citation: Am J Epidemiol. 1994 Jan 1;139(1):16-29
references.pmid: 8296771
references.citation: J Comput Biol. 1997 Fall;4(3):311-23
references.pmid: 9278062
references.citation: J Natl Cancer Inst. 2006 Apr 19;98(8):508-10
references.pmid: 16622115
references.citation: Miner Electrolyte Metab. 1999 Jul-Dec;25(4-6):345-8
references.pmid: 10681664
references.citation: Hum Hered. 2003;56(1-3):18-31
references.pmid: 14614235
references.citation: Cancer Epidemiol Biomarkers Prev. 2000 Oct;9(10):1059-65
references.pmid: 11045788
references.citation: Cancer Chemother Pharmacol. 2006 Jan;57(2):234-40
references.pmid: 16180015
references.citation: Science. 2002 Aug 9;297(5583):1007-13
references.pmid: 12114529
references.citation: Int J Epidemiol. 1980 Sep;9(3):227-31
references.pmid: 7440046
references.citation: Cancer Res. 1997 Jan 1;57(1):75-80
references.pmid: 8988044
references.citation: Nutr Cancer. 2002;43(1):39-46
references.pmid: 12467133
references.citation: Nutr Cancer. 2004;48(2):115-23
references.pmid: 15231446
references.citation: Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16899-903
references.pmid: 12477932
references.citation: Circ Cardiovasc Genet. 2009 Apr;2(2):199-204
references.pmid: 20031585
references.citation: Trends Genet. 1999 Sep;15(9):378
references.pmid: 10461207
references.citation: Am J Epidemiol. 1996 May 1;143(9):907-17
references.pmid: 8610704
references.citation: Mol Cell Endocrinol. 2002 Nov 29;197(1-2):1-13
references.pmid: 12431790
references.citation: J Nutr. 2005 Feb;135(2):252-9
references.pmid: 15671222
references.citation: Cancer Epidemiol Biomarkers Prev. 2008 Oct;17(10):2800-7
references.pmid: 18843026
references.citation: J Natl Cancer Inst. 1999 Jan 20;91(2):176-81
references.pmid: 9923860
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Apr;13(4):546-52
references.pmid: 15066918
references.citation: Trends Genet. 2006 Mar;22(3):119-22
references.pmid: 16430990