SRD5A gene polymorphism in Japanese men predicts prognosis of metastatic prostate cancer with androgen-deprivation therapy

masaki shiota, Naohiro Fujimoto, Akira Yokomizo, ario takeuchi, Momoe Itsumi, Junichi Inokuchi, Katsunori Tatsugami, Takeshi Uchiumi, Seiji Naito

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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 languageEnglish
Article number9525
Pages (from-to)1962-1969
Number of pages8
JournalEuropean Journal of Cancer
Volume51
Issue number14
DOIs
Publication statusPublished - Jun 17 2015

Fingerprint

Androgens
Prostatic Neoplasms
Castration
Genes
Therapeutics
Oxidoreductases
Genotype
Confidence Intervals
Survival
Dihydrotestosterone
Testosterone
Biomarkers

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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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 journalArticle

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title = "SRD5A gene polymorphism in Japanese men predicts prognosis of metastatic prostate cancer with androgen-deprivation therapy",
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.",
author = "masaki shiota and Naohiro Fujimoto and Akira Yokomizo and ario takeuchi and Momoe Itsumi and Junichi Inokuchi and Katsunori Tatsugami and Takeshi Uchiumi and Seiji Naito",
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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

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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.

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JF - European Journal of Cancer and Clinical Oncology

SN - 0959-8049

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