title: Vitamin D receptor polymorphisms and breast cancer risk: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.
abstract: BACKGROUND
  Vitamin D is hypothesized to lower the risk of breast cancer by inhibiting cell proliferation via the nuclear vitamin D receptor (VDR). Two common single nucleotide polymorphisms (SNP) in the VDR gene (VDR), rs1544410 (BsmI), and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokI ff genotype, which encodes a less transcriptionally active isoform of VDR, and reduced risk has been reported for the BsmI BB genotype, a SNP in strong linkage disequilibrium with a 3'-untranslated region, which may influence VDR mRNA stability.
  
  
  METHODS
  We pooled data from 6 prospective studies in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium to examine associations between these SNPs and breast cancer among >6,300 cases and 8,100 controls for each SNP using conditional logistic regression.
  
  
  RESULTS
  The odds ratio (OR) for the rs2228570 (FokI) ff versus FF genotype in the overall population was statistically significantly elevated [OR, 1.16; 95% confidence interval (95% CI), 1.04-1.28] but was weaker once data from the cohort with previously published positive findings were removed (OR, 1.10; 95% CI, 0.98-1.24). No association was noted between rs1544410 (BsmI) BB and breast cancer risk overall (OR, 0.98; 95% CI, 0.89-1.09), but the BB genotype was associated with a significantly lower risk of advanced breast cancer (OR, 0.74; 95% CI, 0.60-0.92).
  
  
  CONCLUSIONS
  Although the evidence for independent contributions of these variants to breast cancer susceptibility remains equivocal, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status.
authors.affiliation: IARC, Lyon, France.
authors.forename: James D
authors.initials: JD
authors.lastname: McKay
authors.forename: Marjorie L
authors.initials: ML
authors.lastname: McCullough
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Saltzman
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Christine D
authors.initials: CD
authors.lastname: Berg
authors.forename: Goran
authors.initials: G
authors.lastname: Bergland
authors.forename: Sheila
authors.initials: S
authors.lastname: Bingham
authors.forename: Magritt
authors.initials: M
authors.lastname: Brustad
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Laurie
authors.initials: L
authors.lastname: Burdette
authors.forename: Julie
authors.initials: J
authors.lastname: Buring
authors.forename: Eugenia E
authors.initials: EE
authors.lastname: Calle
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: David G
authors.initials: DG
authors.lastname: Cox
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
authors.forename: Heather Spencer
authors.initials: HS
authors.lastname: Feigelson
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Anika
authors.initials: A
authors.lastname: Husing
authors.forename: Rudolph
authors.initials: R
authors.lastname: Kaaks
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Jakob
authors.initials: J
authors.lastname: Linseisen
authors.forename: Catherine A
authors.initials: CA
authors.lastname: McCarty
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Mark P
authors.initials: MP
authors.lastname: Purdue
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Stevens
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Yuenger
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thun
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000235:genetics*; D012306:Risk
chemical_list: D018167:Receptors, Calcitriol