title: Genetic polymorphisms in androgen receptor-binding sites predict survival in prostate cancer patients receiving androgen-deprivation therapy.
abstract: BACKGROUND
  Activated androgen receptor binds to androgen-responsive elements (AREs) in genome to regulate target gene transcription and, consequently, mediates physiological or tumorigenic processes of the prostate. Our aim was to determine whether genetic variants in AREs are associated with clinical outcomes after androgen-deprivation therapy (ADT) in prostate cancer patients.
  
  
  METHODS
  We systematically investigated 55 common single-nucleotide polymorphisms (SNPs) in the genome-wide insilico-predicted AREs in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT was assessed by Kaplan-Meier analysis and Cox regression model.
  
  
  RESULTS
  In univariate analysis, two, five, and four SNPs were associated with disease progression, PCSM, and ACM, respectively. After adjusting for known prognostic factors, ARRDC3 rs2939244, FLT1 rs9508016, and SKAP1 rs6504145 remained as significant predictors for PCSM and FBXO32 rs7830622 and FLT1 rs9508016 remained as significant predictors for ACM in multivariate analysis. Moreover, strong combined genotype effects on PCSM and ACM were also observed (P(trend) < 0.001).
  
  
  CONCLUSIONS
  Our results suggest that SNPs in AREs influence prostate cancer survival and may further advance our understanding of the disease progression.
authors.affiliation: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung.
authors.forename: C-N
authors.initials: CN
authors.lastname: Huang
authors.affiliation: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung; Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung; Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung.
authors.forename: S-P
authors.initials: SP
authors.lastname: Huang
authors.affiliation: Department of Pharmacy Practice, Tri-Service General Hospital, Taipei.
authors.forename: J-B
authors.initials: JB
authors.lastname: Pao
authors.affiliation: Departments of Occupational Safety and Health.
authors.forename: T-Y
authors.initials: TY
authors.lastname: Chang
authors.affiliation: Departments of Pharmacy, China Medical University, Taichung.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Lan
authors.affiliation: Departments of Pharmacy, China Medical University, Taichung.
authors.forename: T-L
authors.initials: TL
authors.lastname: Lu
authors.affiliation: Departments of Pharmacy, China Medical University, Taichung.
authors.forename: H-Z
authors.initials: HZ
authors.lastname: Lee
authors.affiliation: Departments of Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung.
authors.forename: S-H
authors.initials: SH
authors.lastname: Juang
authors.affiliation: Departments of Pharmacy, China Medical University, Taichung.
authors.forename: P-P
authors.initials: PP
authors.lastname: Wu
authors.affiliation: Department of Urology, National Taiwan University Hospital, Taipei.
authors.forename: Y-S
authors.initials: YS
authors.lastname: Pu
authors.affiliation: Department of Health Care Administration, Oriental Institute of Technology, Taipei; Graduate Institute of Health Care Organization Administration, College of Public Health, National Taiwan University, Taipei.
authors.forename: C-J
authors.initials: CJ
authors.lastname: Hsieh
authors.affiliation: Departments of Pharmacy, China Medical University, Taichung; Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan. Electronic address: bao@mail.cmu.edu.tw.
authors.forename: B-Y
authors.initials: BY
authors.lastname: Bao
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D019390:Arrestins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D011944:Receptors, Androgen / Q000235:genetics*; D020218:Response Elements / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*
chemical_list: C508469:ARRDC3 protein, human; D000726:Androgen Antagonists; D019390:Arrestins; D010750:Phosphoproteins; D011944:Receptors, Androgen; C108336:SKAP1 protein, human; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1