Genetic Polymorphism in Sex Hormone-binding Globulin With a Prognosis of Androgen Deprivation Therapy in Metastatic Prostate Cancer Among Japanese Men
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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DOI：
10.1016/j.clgc.2019.03.021
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发表时间：
2019-06-01
影响因子：
3.2
通讯作者：
Eto, Masatoshi
中科院分区：
文献类型：
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作者：
Shiota, Masaki;Fujimoto, Naohiro;Eto, Masatoshi
本研究调查了104名接受初次雄激素剥夺治疗(ADT)的日本转移性前列腺癌患者中SHBG基因错义多态(rs6259，D356N)的影响。SHBG的基因型与疾病进展和任何原因导致的死亡有关，但与ADT期间的血清睾酮水平无关。本研究提示SHBG变异可能是ADT的一个独立的预后生物标志物。前言：雄激素剥夺治疗(ADT)期间血清睾酮抑制可影响ADT的肿瘤预后。尽管性激素结合球蛋白(SHBG)的遗传变异被报道与血清睾酮水平相关，但在ADT过程中与血清睾酮水平的相关性仍不清楚。因此，这项研究调查了SHBG基因错义多态对接受原发ADT治疗的转移性前列腺癌患者的影响。患者和方法：这项研究包括104名患有转移性前列腺癌的日本男性。研究SHBG基因(rs6259、D356N)多态性与ADT的临床病理参数(包括血清睾酮水平)以及预后(包括无进展生存期和总生存期)的关系。结果：携带SHBG基因纯合子野生型(GG)和杂合子/纯合子变异体(GA/AA)的男性在ADT期间的血清睾酮水平相当。在调整了年龄、Gleason评分、初始前列腺特异性抗原和临床T分期后，SHBG基因的杂合/纯合子变异(GA/AA)与更高的进展风险(风险比，2.20；95%可信区间，1.10-4.18；P=.027)和任何原因死亡(风险比，3.21；95%可信区间，1.31-7.35；P=.012)相关。结论：本研究提示SHBG(Rs6259)基因变异可能是接受原发ADT治疗的转移性前列腺癌患者的一个独立的预后生物标志物。(C)2019 Elsevier Inc.保留所有权利。
This study investigated the impact of a missense polymorphism (rs6259, D356N) in the SHBG gene among 104 Japanese treated with primary androgen deprivation therapy (ADT) for metastatic prostate cancer. Genotype in SHBG was associated with progression and any-cause death, but not with serum testosterone levels during ADT. This study suggested SHBG variation might be an independent prognostic biomarker in ADT.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. (C) 2019 Elsevier Inc. All rights reserved.