Abstract
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.
| Original language | English |
|---|---|
| Article number | 9525 |
| Pages (from-to) | 1962-1969 |
| Number of pages | 8 |
| Journal | European Journal of Cancer |
| Volume | 51 |
| Issue number | 14 |
| DOIs | |
| Publication status | Published - Jun 17 2015 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
SRD5A gene polymorphism in Japanese men predicts prognosis of metastatic prostate cancer with androgen-deprivation therapy. / shiota, masaki; Fujimoto, Naohiro; Yokomizo, Akira; takeuchi, ario; Itsumi, Momoe; Inokuchi, Junichi; Tatsugami, Katsunori; Uchiumi, Takeshi; Naito, Seiji.
In: European Journal of Cancer, Vol. 51, No. 14, 9525, 17.06.2015, p. 1962-1969.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - SRD5A gene polymorphism in Japanese men predicts prognosis of metastatic prostate cancer with androgen-deprivation therapy
AU - shiota, masaki
AU - Fujimoto, Naohiro
AU - Yokomizo, Akira
AU - takeuchi, ario
AU - Itsumi, Momoe
AU - Inokuchi, Junichi
AU - Tatsugami, Katsunori
AU - Uchiumi, Takeshi
AU - Naito, Seiji
PY - 2015/6/17
Y1 - 2015/6/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84939567808&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84939567808&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2015.06.122
DO - 10.1016/j.ejca.2015.06.122
M3 - Article
VL - 51
SP - 1962
EP - 1969
JO - European Journal of Cancer and Clinical Oncology
JF - European Journal of Cancer and Clinical Oncology
SN - 0959-8049
IS - 14
M1 - 9525
ER -