title: SRD5A gene polymorphism in Japanese men predicts prognosis of metastatic prostate cancer with androgen-deprivation therapy.
abstract: OBJECTIVE
  De novo androgen synthesis is thought to be involved in the progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT). During androgen synthesis, 5α-reductase encoded by SRD5A catalyses testosterone into more active dihydrotestosterone and may be involved in the progression to CRPC. Then, this study aimed to reveal the association between genetic variations in SRD5A and the prognosis in metastatic prostate cancer.
  
  
  METHODS
  We studied the polymorphisms rs518673 and rs166050 in SRD5A1, and rs12470143, rs523349, rs676033 and rs2208532 in SRD5A2 as well as the time to CRPC progression and overall survival in 104 patients with metastatic prostate cancer that had undergone primary ADT. The association between the polymorphisms and the progression to CRPC as well as overall survival was examined.
  
  
  RESULTS
  Patients carrying the more active GG genotype in SRD5A2 rs523349 exhibited a higher risk of the progression (hazard ration [95% confidence interval], 1.93 [1.14-3.14], p=0.016) and death (hazard ration [95% confidence interval], 2.14 [1.16-3.76], p=0.016), compared with less active GC/CC genotypes in SRD5A2 rs523349.
  
  
  CONCLUSIONS
  High 5α-reductase activity due to the polymorphism in SRD5A2 may contribute to resistance to ADT. Furthermore, SRD5A2 rs523349 polymorphism may be a promising biomarker for metastatic prostate cancer patients treated with primary ADT and a molecular target for advanced prostate cancer.
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Shiota
authors.affiliation: Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8556, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Fujimoto
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: yokoa@uro.med.kyushu-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Yokomizo
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Ario
authors.initials: A
authors.lastname: Takeuchi
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Momoe
authors.initials: M
authors.lastname: Itsumi
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Inokuchi
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tatsugami
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uchiumi
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005787:Gene Frequency; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D008565:Membrane Proteins; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548467:SRD5A1 protein, human; C548468:SRD5A2 protein, human
keywords: Androgen-deprivation therapy; Castration-resistant prostate cancer; Prostate cancer; SNP; SRD5A