title: Polymorphisms inside microRNAs and microRNA target sites predict clinical outcomes in prostate cancer patients receiving androgen-deprivation therapy.
abstract: OBJECTIVE
  Recent evidence indicates that small noncoding RNA molecules, known as microRNAs (miRNAs), are involved in cancer initiation and progression. We hypothesized that genetic variations in miRNAs and miRNA target sites could be associated with the efficacy of androgen-deprivation therapy (ADT) in men with prostate cancer.
  
  
  METHODS
  We systematically evaluated 61 common single nucleotide polymorphisms (SNPs) inside miRNAs and miRNA target sites 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 were assessed by Kaplan-Meier analysis and Cox regression model.
  
  
  RESULTS
  Four, seven, and four SNPs were significantly associated with disease progression, PCSM, and ACM, respectively, after ADT in univariate analysis. KIF3C rs6728684, CDON rs3737336, and IFI30 rs1045747 genotypes remained as significant predictors for disease progression; KIF3C rs6728684, PALLD rs1071738, GABRA1 rs998754, and SYT9 rs4351800 remained as significant predictors for PCSM; and SYT9 rs4351800 remained as a significant predictor for ACM in multivariate models that included clinicopathologic predictors. Moreover, strong combined genotype effects on disease progression and PCSM were also observed. Patients with a greater number of unfavorable genotypes had a shorter time to progression and worse prostate cancer-specific survival during ADT (P for trend < 0.001).
  
  
  CONCLUSIONS
  SNPs inside miRNAs and miRNA target sites have a potential value to improve outcome prediction in prostate cancer patients receiving ADT.
authors.affiliation: Department of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Bo-Ying
authors.initials: BY
authors.lastname: Bao
authors.forename: Jiunn-Bey
authors.initials: JB
authors.lastname: Pao
authors.forename: Chun-Nung
authors.initials: CN
authors.lastname: Huang
authors.forename: Yeong-Shiau
authors.initials: YS
authors.lastname: Pu
authors.forename: Ta-Yuan
authors.initials: TY
authors.lastname: Chang
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Lan
authors.forename: Te-Ling
authors.initials: TL
authors.lastname: Lu
authors.forename: Hong-Zin
authors.initials: HZ
authors.lastname: Lee
authors.forename: Shin-Hun
authors.initials: SH
authors.lastname: Juang
authors.forename: Lu-Min
authors.initials: LM
authors.lastname: Chen
authors.forename: Chi-Jeng
authors.initials: CJ
authors.lastname: Hsieh
authors.forename: Shu-Pin
authors.initials: SP
authors.lastname: Huang
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D056726:Genetic Association Studies; D005838:Genotype; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009919:Orchiectomy; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000628:therapy; D034622:RNA Interference; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D035683:MicroRNAs; D007987:Gonadotropin-Releasing Hormone