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.
| Original language | English |
|---|---|
| Pages (from-to) | 734-740 |
| Number of pages | 7 |
| Journal | Journal of Urology |
| Volume | 199 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 1 2018 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Urology
Cite this
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. / shiota, masaki; Fujimoto, Naohiro; takeuchi, ario; Kashiwagi, Eiji; Dejima, Takashi; Inokuchi, Junichi; Tatsugami, Katsunori; Yokomizo, Akira; Kajioka, Shunichi; Uchiumi, Takeshi; Eto, Masatoshi.
In: Journal of Urology, Vol. 199, No. 3, 01.03.2018, p. 734-740.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - shiota, masaki
AU - Fujimoto, Naohiro
AU - takeuchi, ario
AU - Kashiwagi, Eiji
AU - Dejima, Takashi
AU - Inokuchi, Junichi
AU - Tatsugami, Katsunori
AU - Yokomizo, Akira
AU - Kajioka, Shunichi
AU - Uchiumi, Takeshi
AU - Eto, Masatoshi
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85040691476&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040691476&partnerID=8YFLogxK
U2 - 10.1016/j.juro.2017.09.076
DO - 10.1016/j.juro.2017.09.076
M3 - Article
C2 - 28941922
AN - SCOPUS:85040691476
VL - 199
SP - 734
EP - 740
JO - Journal of Urology
JF - Journal of Urology
SN - 0022-5347
IS - 3
ER -