title: Association of variants in estrogen-related pathway genes with prostate cancer risk.
abstract: BACKGROUND
  Through mediation of estrogen receptors, estradiol has been shown to have both carcinogenic and anti-carcinogenic effects on the prostate. We performed a population-based case-control study to investigate variants in estrogen-related genes ESR1, ESR2, CYP19A1, CYP1A1, and CYP1B1 and the potential association with risk of prostate cancer (PCa).
  
  
  METHODS
  We evaluated PCa risk conferred by 73 single nucleotide polymorphisms in 1,304 incident PCa cases and 1,266 age-matched controls. Analysis included stratification by clinical features and assessment of environmental modifiers.
  
  
  RESULTS
  There was evidence of altered risk of developing PCa for variants in ESR1, CYP1A1, and CYP1B1, however, only CYP1B1 rs1056836 retained significance after adjustment for multiple comparisons. An association with risk for more aggressive PCa was observed for variants in ESR1, ESR2, and CYP19A1, but none was significant after adjustment for multiple comparisons. There was no effect modification by obesity.
  
  
  CONCLUSIONS
  Germline genetic variation of these estrogen pathway genes may contribute to risk of PCa. Additional studies to validate these results and examine the functional consequence of validated variants are warranted.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. skholt@fhcrc.org
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Holt
authors.forename: Erika M
authors.initials: EM
authors.lastname: Kwon
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kolb
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stanford
mesh_terms: D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D004843:Epistasis, Genetic; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012307:Risk Factors
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D001189:Aryl Hydrocarbon Hydroxylases; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1