Masaki Shiota1, Naohiro Fujimoto2, Shigehiro Tsukahara3, Miho Ushijima4, Ario Takeuchi4, Eiji Kashiwagi4, Junichi Inokuchi4, Katsunori Tatsugami4, Takeshi Uchiumi5, Masatoshi Eto4. 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; Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 4. Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 5. Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Abstract
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.
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.