Circulating steroid hormones and the risk of prostate cancer
Circulating steroid hormones and the risk of prostate cancer
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DOI：
10.1158/1055-9965.epi-05-0633
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发表时间：
2006-01-01
影响因子：
3.8
通讯作者：
Giles, GG
中科院分区：
文献类型：
--
作者：
Severi, G;Morris, HA;Giles, GG
流行病学研究未能支持循环中的雄激素与前列腺癌风险正相关的假设，最近的一些研究甚至表明，高水平的睾酮可能具有保护作用，特别是对侵袭性癌症。在一项17,049名男性的前瞻性队列研究中，我们通过测量基线收集的血浆中总睾酮、雄烯二酮、雄烯二酮、DHEA硫酸盐、雌二醇和性激素结合球蛋白来检验这一假设。我们使用了病例队列设计，包括在平均8.7年的随访中诊断出的524例病例和随机抽样的1,859名男性亚队列。每种荷尔蒙水平与前列腺癌风险之间的关联通过对出生国家进行校正的COX模型进行了检验。雌二醇浓度加倍，患前列腺癌的风险降低30%，但证据很弱(P-趋势=0.07)。其他激素均与前列腺癌无关(P-Trend>；=0.3)。没有一种激素与非侵袭性前列腺癌有关(所有P趋势=0.2)。当睾酮(HR，0.55；95%CI，0.32-0.95)和雄烯二酮(HR，0.51；95%CI，0.31-0.83)浓度加倍时，侵袭性癌症的风险比几乎减半，而DHEA硫酸盐浓度加倍(HR，0.63；95%CI，0.46-0.87)，风险比降低37%。游离睾酮、雌二醇和性激素结合球蛋白在患侵袭性癌症的风险方面也有类似的负向但不显著的线性趋势(P趋势分别为0.06、0.2和0.1)。因此，高水平的睾酮和肾上腺雄激素与侵袭性前列腺癌风险的降低有关，但与非侵袭性疾病无关。
Epidemiologic studies have failed to support the hypothesis that circulating androgens are positively associated with prostate cancer risk and some recent studies have even suggested that high testosterone levels might be protective particularly against aggressive cancer. We tested this hypothesis by measuring total testosterone, androstanediol glucuronide, androstenedione, DHEA sulfate, estradiol, and sex hormone-binding globulin in plasma collected at baseline in a prospective cohort study of 17,049 men. We used a case-cohort design, including 524 cases diagnosed during a mean 8.7 years follow-up and a randomly sampled subcohort of 1,859 men. The association between each hormone level and prostate cancer risk was tested using Cox models adjusted for country of birth. The risk of prostate cancer was similar to 30% lower for a doubling of the concentration of estradiol but the evidence was weak (P-trend = 0.07). None of the other hormones was associated with overall prostate cancer (P-trend >= 0.3). None of the hormones was associated with nonaggressive prostate cancer (all P-trend = 0.2). The hazard ratio [HR; 95% confidence interval (95% CI)]r aggressive cancer almost halved for a doubling of the concentration of testosterone (HR, 0.55; 95% CI, 0.32-0.95) and androstenedione (HR, 0.51; 95% CI 0.31-0.83), and was 37% lower for a doubling of the concentration of DHEA sulfate (HR, 0.63; 95% CI, 0.46-0.87). Similar negative but nonsignificant linear trends in risk for aggressive cancer were obtained for free testosterone, estradiol, and sex hormone-binding globulin (P-trend = 0.06, 0.2, and 0.1, respectively). High levels of testosterone and adrenal androgens are thus associated with reduced risk of aggressive prostate cancer but not with nonaggressive disease.