Genetic Polymorphism in Sex Hormone-binding Globulin With a Prognosis of Androgen Deprivation Therapy in Metastatic Prostate Cancer Among Japanese Men |
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Authors: | Masaki Shiota Naohiro Fujimoto Shigehiro Tsukahara Miho Ushijima Ario Takeuchi Eiji Kashiwagi Junichi Inokuchi Katsunori Tatsugami Takeshi Uchiumi Masatoshi Eto |
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Affiliation: | 1. Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;2. Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan;3. Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan |
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Abstract: | IntroductionTestosterone 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 MethodsThis 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.ResultsThe 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).ConclusionsThis 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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Keywords: | Address for correspondence: Masaki Shiota, MD, PhD, Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan Castration resistance Ethnics Hormone therapy Prognostic factor Testosterone |
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