Relationships between Circulating and Intraprostatic Sex Steroid Hormone Concentrations.
Relationships between Circulating and Intraprostatic Sex Steroid Hormone Concentrations.
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DOI：
10.1158/1055-9965.epi-17-0215
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发表时间：
2017-11
期刊：
影响因子：
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通讯作者：
Hsing AW
中科院分区：
文献类型：
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作者：
Cook MB;Stanczyk FZ;Wood SN;Pfeiffer RM;Hafi M;Veneroso CC;Lynch B;Falk RT;Zhou CK;Niwa S;Emanuel E;Gao YT;Hemstreet GP;Zolfghari L;Carroll PR;Manyak MJ;Sesterhann IA;Levine PH;Hsing AW
性激素与前列腺癌的发生有关，但流行病学研究没有提供确凿的证据。我们测试的假设，性类固醇激素的循环浓度反映前列腺内浓度使用血清和相邻的显微镜证实的前列腺癌病例的良性前列腺组织。计划手术的局部前列腺癌病例被邀请参加。获得许可的参与者完成了调查，并提供了切除的组织和血液。新鲜冷冻组织末端的组织学评估证实了邻近的经显微镜验证的良性病理。血清和组织中的性类固醇激素被提取，色谱分离，然后用放射免疫测定法定量。使用线性回归来解释前列腺内激素浓度随年龄、体重指数、种族和研究地点的变化，并随后评估与血清激素浓度的关系。Gleason评分（来自相邻肿瘤组织）、种族和年龄被评估为潜在的效应修饰因子。循环中的性类固醇激素浓度与前列腺内性类固醇激素浓度有低至中度的相关性，并解释了小比例的变化。雄甾烷-3 α，17 β-二醇葡糖苷酸（3 α-二醇G）解释了3 α-二醇G组织浓度的最大方差（线性回归r2 = 0.21），其次是血清睾酮和组织二氢睾酮（r2 = 0.10），然后是血清雌酮和组织雌酮（r2 = 0.09）。Gleason评分、人种或年龄对疗效无影响。性类固醇激素的循环浓度是前列腺内激素环境的不良替代措施。前列腺内循环性类固醇激素浓度提供的高暴露错误分类可能部分解释了循环激素与前列腺癌风险缺乏任何一致的相关性。
Sex hormones have been implicated in prostate carcinogenesis, yet epidemiological studies have not provided substantiating evidence. We tested the hypothesis that circulating concentrations of sex steroid hormones reflect intraprostatic concentrations using serum and adjacent microscopically-verified benign prostate tissue from prostate cancer cases. Incident localized prostate cancer cases scheduled for surgery were invited to participate. Consented participants completed surveys, and provided resected tissues and blood. Histologic assessment of the ends of fresh frozen tissue confirmed adjacent microscopically-verified benign pathology. Sex steroid hormones in sera and tissues were extracted, chromatographically separated, and then quantitated by radioimmunoassays. Linear regression was used to account for variations in intraprostatic hormone concentrations by age, body mass index, race and study site, and subsequently to assess relationships with serum hormone concentrations. Gleason score (from adjacent tumor tissue), race and age were assessed as potential effect modifiers. Circulating sex steroid hormone concentrations had low-to-moderate correlations with—and explained small proportions of variations in—intraprostatic sex steroid hormone concentrations. Androstane-3α,17β-diol glucuronide (3α-diol G) explained the highest variance of tissue concentrations of 3α-diol G (linear regression r2=0.21), followed by serum testosterone and tissue dihydrotestosterone (r2=0.10), and then serum estrone and tissue estrone (r2=0.09). There was no effect modification by Gleason score, race or age. Circulating concentrations of sex steroid hormones are poor surrogate measures of the intraprostatic hormonal milieu. The high exposure misclassification provided by circulating sex steroid hormone concentrations for intraprostatic levels may partly explain the lack of any consistent association of circulating hormones with prostate cancer risk.