The Association of Polymorphisms in the Gene Encoding Gonadotropin-Releasing Hormone with Serum Testosterone Level during Androgen Deprivation Therapy and Prognosis of Metastatic Prostate Cancer.

Autor:	Shiota M; Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: shiota@uro.med.kyushu-u.ac.jp., Fujimoto N; Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan., Takeuchi A; Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Kashiwagi E; Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Dejima T; Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Inokuchi J; Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Tatsugami K; Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Yokomizo A; Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Kajioka S; Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Uchiumi T; Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Eto M; Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Jazyk:	angličtina
Zdroj:	The Journal of urology [J Urol] 2018 Mar; Vol. 199 (3), pp. 734-740. Date of Electronic Publication: 2017 Sep 20.
DOI:	10.1016/j.juro.2017.09.076
Abstrakt:	Purpose: Serum testosterone suppression during androgen deprivation therapy has been reported to affect the efficacy of androgen deprivation therapy. However, the factors impacting hormonal variations during androgen deprivation therapy remain unclear. Therefore, in this study we investigated the significance of missense polymorphisms in the gene encoding GNRH in men treated with primary androgen deprivation therapy for metastatic prostate cancer. Materials and Methods: This study included 80 Japanese patients with metastatic prostate cancer with available serum testosterone levels during androgen deprivation therapy. We examined the association of GNRH1 (rs6185, S20W) and GNRH2 (rs6051545, A16V) gene polymorphisms with clinicopathological parameters, including serum testosterone levels during androgen deprivation therapy, as well as prognosis, including progression-free and overall survival. Results: The CT and CT/TT alleles in the GNRH2 gene (rs6051545) were associated with higher serum testosterone during androgen deprivation therapy compared with those of the CC allele. Consequently the CT alleles were associated with a higher risk of progression after adjustment for age and serum testosterone during androgen deprivation therapy (HR 1.73, 95% CI 1.00-3.00, p = 0.049). Conclusions: Taken together these findings suggest that rs6051545 (GNRH2) genetic variation may result in inadequate suppression of serum testosterone during androgen deprivation therapy. This may lead to detrimental effects of androgen deprivation therapy on prognosis in men with metastatic prostate cancer. (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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