title: Genetic variation in the vitamin d pathway in relation to risk of prostate cancer--results from the breast and prostate cancer cohort consortium.
abstract: BACKGROUND
  Studies suggest that vitamin D status may be associated with prostate cancer risk although the direction and strength of this association differs between experimental and observational studies. Genome-wide association studies have identified genetic variants associated with 25-hydroxyvitamin D [25(OH)D] status. We examined prostate cancer risk in relation to single-nucleotide polymorphisms (SNP) in four genes shown to predict circulating levels of 25(OH)D.
  
  
  METHODS
  SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped in 10,018 cases and 11,052 controls from the National Cancer Institute (NCI) Breast and Prostate Cancer Cohort Consortium. Logistic regression was used to estimate the individual and cumulative association between genetic variants and risk of overall and aggressive prostate cancer.
  
  
  RESULTS
  We observed a decreased risk of aggressive prostate cancer among men with the allele in rs6013897 near CYP24A1 associated with lower serum 25(OH)D [per A allele, OR, 0.86; 95% confidence interval (CI), 0.80-0.93; Ptrend = 0.0002) but an increased risk for nonaggressive disease (per A allele: OR, 1.10; 95% CI, 1.04-1.17; Ptrend = 0.002). Examination of a polygenic score of the four SNPs revealed statistically significantly lower risk of aggressive prostate cancer among men with a greater number of low vitamin D alleles (OR for 6-8 vs. 0-1 alleles, 0.66; 95% CI, 0.44-0.98; Ptrend = 0.003).
  
  
  CONCLUSIONS
  In this large, pooled analysis, genetic variants related to lower 25(OH)D levels were associated with a decreased risk of aggressive prostate cancer.
  
  
  CONCLUSIONS
  Our genetic findings do not support a protective association between loci known to influence vitamin D levels and prostate cancer risk.
authors: National Cancer Institute, NIH, 6120 Executive Blvd, Suite 320, Rockville, MD 20852, USA. mondulam@mail.nih.gov
authors: Alison M
authors: AM
authors: Mondul
authors: Irene M
authors: IM
authors: Shui
authors: Kai
authors: K
authors: Yu
authors: Ruth C
authors: RC
authors: Travis
authors: Victoria L
authors: VL
authors: Stevens
authors: Daniele
authors: D
authors: Campa
authors: Frederick R
authors: FR
authors: Schumacher
authors: Regina G
authors: RG
authors: Ziegler
authors: H Bas
authors: HB
authors: Bueno-de-Mesquita
authors: Sonja
authors: S
authors: Berndt
authors: E D
authors: ED
authors: Crawford
authors: Susan M
authors: SM
authors: Gapstur
authors: J Michael
authors: JM
authors: Gaziano
authors: Edward
authors: E
authors: Giovannucci
authors: Christopher A
authors: CA
authors: Haiman
authors: Brian E
authors: BE
authors: Henderson
authors: David J
authors: DJ
authors: Hunter
authors: Mattias
authors: M
authors: Johansson
authors: Timothy J
authors: TJ
authors: Key
authors: Loïc
authors: L
authors: Le Marchand
authors: Sara
authors: S
authors: Lindström
authors: Marjorie L
authors: ML
authors: McCullough
authors: Carmen
authors: C
authors: Navarro
authors: Kim
authors: K
authors: Overvad
authors: Domenico
authors: D
authors: Palli
authors: Mark
authors: M
authors: Purdue
authors: Meir J
authors: MJ
authors: Stampfer
authors: Stephanie J
authors: SJ
authors: Weinstein
authors: Walter C
authors: WC
authors: Willett
authors: Meredith
authors: M
authors: Yeager
authors: Stephen J
authors: SJ
authors: Chanock
authors: Dimitrios
authors: D
authors: Trichopoulos
authors: Laurence N
authors: LN
authors: Kolonel
authors: Peter
authors: P
authors: Kraft
authors: Demetrius
authors: D
authors: Albanes
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D053493:Cholestanetriol 26-Monooxygenase / Q000097:blood / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000097:blood / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood / Q000209:etiology*; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000097:blood / Q000235:genetics; D014807:Vitamin D / Q000097:blood*; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D014408:Biomarkers, Tumor; D014807:Vitamin D; D013250:Steroid Hydroxylases; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase
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