TY - JOUR
T1 - Genetic Polymorphism in Sex Hormone-binding Globulin With a Prognosis of Androgen Deprivation Therapy in Metastatic Prostate Cancer Among Japanese Men
AU - Shiota, Masaki
AU - Fujimoto, Naohiro
AU - Tsukahara, Shigehiro
AU - Ushijima, Miho
AU - Takeuchi, Ario
AU - Kashiwagi, Eiji
AU - Inokuchi, Junichi
AU - Tatsugami, Katsunori
AU - Uchiumi, Takeshi
AU - Eto, Masatoshi
N1 - Funding Information:
The authors would like to thank Ms. Noriko Hakoda and Ms. Eriko Gunshima for technical assistance. The authors thank Edanz Group ( www.edanzediting.com/ac ) for editing a draft of this manuscript. This work was supported by a Medical Research Promotion Grant from JSPS KAKENHI grant ( 17K11145 ).
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/6
Y1 - 2019/6
N2 - Introduction: Testosterone suppression in serum during androgen deprivation therapy (ADT) can affect the oncologic outcome of ADT. Although genetic variants in sex hormone-binding globulin (SHBG) were reported to be correlated with serum testosterone level, the association with serum testosterone during ADT remains unclear. Therefore, this study investigated the impact of a missense polymorphism in the SHBG gene among men treated with primary ADT for metastatic prostate cancer. Patients and Methods: This study included 104 Japanese men with metastatic prostate cancer. The association of SHBG gene polymorphism (rs6259, D356N) with clinicopathologic parameters including serum testosterone levels during ADT, as well as prognosis, including progression-free survival and overall survival, was examined. Results: The serum testosterone levels during ADT were comparable between men carrying the homozygous wild-type (GG) and heterozygous/homozygous variant (GA/AA) in the SHBG gene. When adjusted for age, Gleason score, initial prostate-specific antigen, and clinical T-stage, the heterozygous/homozygous variant (GA/AA) in the SHBG gene was associated with a higher risk of progression (hazard ratio, 2.20; 95% confidence interval, 1.10-4.18; P =.027) and any-cause death (hazard ratio, 3.21; 95% confidence interval, 1.31-7.35; P =.012). Conclusions: This study suggested genetic variation in SHBG (rs6259) might be an independent prognostic biomarker among men treated with primary ADT for metastatic prostate cancer.
AB - Introduction: Testosterone suppression in serum during androgen deprivation therapy (ADT) can affect the oncologic outcome of ADT. Although genetic variants in sex hormone-binding globulin (SHBG) were reported to be correlated with serum testosterone level, the association with serum testosterone during ADT remains unclear. Therefore, this study investigated the impact of a missense polymorphism in the SHBG gene among men treated with primary ADT for metastatic prostate cancer. Patients and Methods: This study included 104 Japanese men with metastatic prostate cancer. The association of SHBG gene polymorphism (rs6259, D356N) with clinicopathologic parameters including serum testosterone levels during ADT, as well as prognosis, including progression-free survival and overall survival, was examined. Results: The serum testosterone levels during ADT were comparable between men carrying the homozygous wild-type (GG) and heterozygous/homozygous variant (GA/AA) in the SHBG gene. When adjusted for age, Gleason score, initial prostate-specific antigen, and clinical T-stage, the heterozygous/homozygous variant (GA/AA) in the SHBG gene was associated with a higher risk of progression (hazard ratio, 2.20; 95% confidence interval, 1.10-4.18; P =.027) and any-cause death (hazard ratio, 3.21; 95% confidence interval, 1.31-7.35; P =.012). Conclusions: This study suggested genetic variation in SHBG (rs6259) might be an independent prognostic biomarker among men treated with primary ADT for metastatic prostate cancer.
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U2 - 10.1016/j.clgc.2019.03.021
DO - 10.1016/j.clgc.2019.03.021
M3 - Article
C2 - 31036465
AN - SCOPUS:85064742147
VL - 17
SP - e387-e393
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
SN - 1558-7673
IS - 3
ER -
