Fujimoto Naohiro
   Department   School of Medicine  Urology, Clinical Medical Sciences
   Position  
Article types journal article
Language English
Peer review Non peer reviewed
Title SRD5A gene polymorphism in Japanese men predicts prognosis of metastatic prostate cancer with androgen-deprivation therapy.
Journal Formal name:European journal of cancer (Oxford, England : 1990)
Abbreviation:Eur J Cancer
ISSN code:18790852/09598049
Domestic / ForeginForegin
Volume, Issue, Page 51(14),1962-9頁
Author and coauthor Shiota Masaki, Fujimoto Naohiro, Yokomizo Akira, Takeuchi Ario, Itsumi Momoe, Inokuchi Junichi, Tatsugami Katsunori, Uchiumi Takeshi, Naito Seiji
Publication date 2015/09
Summary AIM: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.
DOI 10.1016/j.ejca.2015.06.122
PMID 26169017