Masaki Shiota1, Naohiro Fujimoto2, Ario Takeuchi3, Eiji Kashiwagi3, Takashi Dejima3, Junichi Inokuchi3, Katsunori Tatsugami3, Akira Yokomizo3, Shunichi Kajioka3, Takeshi Uchiumi4, Masatoshi Eto3. 1. Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: shiota@uro.med.kyushu-u.ac.jp. 2. Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. 3. Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 4. Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Abstract
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.
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.
Authors: Jacklyn N Hellwege; Sarah Stallings; Eric S Torstenson; Robert Carroll; Kenneth M Borthwick; Murray H Brilliant; David Crosslin; Adam Gordon; George Hripcsak; Gail P Jarvik; James G Linneman; Parimala Devi; Peggy L Peissig; Patrick A M Sleiman; Hakon Hakonarson; Marylyn D Ritchie; Shefali Setia Verma; Ning Shang; Josh C Denny; Dan M Roden; Digna R Velez Edwards; Todd L Edwards Journal: Sci Rep Date: 2019-04-15 Impact factor: 4.379