title: Vitamin D-related gene polymorphisms, plasma 25-hydroxyvitamin D, and breast cancer risk.
abstract: OBJECTIVE
  Studies of vitamin D-pathway genetic variants in relation to cancer risk have been inconsistent. We examined the associations between vitamin D-related genetic polymorphisms, plasma 25-hydroxyvitamin D [25(OH)D], and breast cancer risk.
  
  
  METHODS
  In a population-based case-control study of 967 incident breast cancer cases and 993 controls, we genotyped 25 polymorphisms encoding the vitamin D receptor (VDR) gene, 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), and vitamin D-binding protein (GC) and measured plasma 25(OH)D. We used multivariable logistic regression to estimate adjusted odds ratios (ORs) and 95 % confidence intervals (CIs).
  
  
  RESULTS
  Among CYP24A1 polymorphisms, rs6068816 was associated with a 72 % reduction in breast cancer risk (TT vs. CC, OR 0.28, 95 % CI 0.10-0.76; p trend = 0.01), but for rs13038432, the 46 % decrease included the null value (GG vs. AA, OR 0.54, 95 % CI 0.17-1.67; p trend = 0.03). Increased risk that included the null value was noted for CYP24A1 rs3787557 (CC vs. TT, OR 1.34, 95 % CI 0.92-1.89). The VDR polymorphism, TaqI (rs731236), was associated with a 26 % risk reduction (TT vs. CC, OR 0.74, 95 % CI 0.56-0.98; p trend = 0.01). For other polymorphisms, ORs were weak and included the null value. The inverse association for plasma 25(OH)D with breast cancer was more pronounced (OR 0.43, 95 % CI 0.27-0.68) among women with the common allele for CYP24A1, rs927650 (p for interaction on a multiplicative scale = 0.01).
  
  
  CONCLUSIONS
  Breast cancer risk may be associated with specific vitamin D-related polymorphisms, particularly CYP24A1. Genetic variation in the vitamin D pathway should be considered when designing potential intervention strategies with vitamin D supplementation.
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 W 168th St, 7th Floor, New York, NY, 10032, USA. llr2124@columbia.edu.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Reimers
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 W 168th St, 7th Floor, New York, NY, 10032, USA.|Department of Medicine, Columbia University, New York, NY, USA.|Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Crew
authors.affiliation: Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Bradshaw
authors.affiliation: Department of Environmental Health, Columbia University, New York, NY, USA.|Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.affiliation: Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Steck
authors.affiliation: Department of Environmental Health, Columbia University, New York, NY, USA.
authors.forename: Iryna
authors.initials: I
authors.lastname: Sirosh
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 W 168th St, 7th Floor, New York, NY, 10032, USA.|Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Terry
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 W 168th St, 7th Floor, New York, NY, 10032, USA.|Department of Medicine, Columbia University, New York, NY, USA.|Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
authors.forename: Dawn L
authors.initials: DL
authors.lastname: Hershman
authors.affiliation: Department of Medicine, Columbia University, New York, NY, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Shane
authors.affiliation: Department of Medicine, Columbia University, New York, NY, USA.
authors.forename: Serge
authors.initials: S
authors.lastname: Cremers
authors.affiliation: Department of Medicine, Columbia University, New York, NY, USA.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Dworakowski
authors.affiliation: Department of Preventive Medicine, Mt. Sinai School of Medicine, New York, NY, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Teitelbaum
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 W 168th St, 7th Floor, New York, NY, 10032, USA.|Department of Medicine, Columbia University, New York, NY, USA.|Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
authors.forename: Alfred I
authors.initials: AI
authors.lastname: Neugut
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics*; D002112:Calcifediol / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D012306:Risk; D013250:Steroid Hydroxylases / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000235:genetics; D014809:Vitamin D-Binding Protein / Q000235:genetics*; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics*; D014815:Vitamins
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014809:Vitamin D-Binding Protein; D014815:Vitamins; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C000600378:CYP27B1 protein, human; D002112:Calcifediol