Circulating insulin-like growth factor-I, total and free testosterone concentrations and prostate cancer risk in 200 000 men in UK Biobank.
Circulating insulin-like growth factor-I, total and free testosterone concentrations and prostate cancer risk in 200 000 men in UK Biobank.
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英国生物库中20万名男性的循环胰岛素样生长因子-I、总睾酮和游离睾酮浓度与前列腺癌风险
DOI：
10.1002/ijc.33416
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发表时间：
2021-05-01
影响因子：
6.4
通讯作者：
Travis RC
中科院分区：
文献类型：
--
作者：
Watts EL;Fensom GK;Smith Byrne K;Perez-Cornago A;Allen NE;Knuppel A;Gunter MJ;Holmes MV;Martin RM;Murphy N;Tsilidis KK;Yeap BB;Key TJ;Travis RC
胰岛素样生长因子-I (IGF-I) 和睾酮与前列腺癌病因有关。利用来自大型前瞻性全队列标准化检测和重复血液测量的数据以及来自国际联盟的遗传数据，我们研究了循环 IGF-I、性激素结合球蛋白 (SHBG) 以及总游离睾酮浓度和计算的游离睾酮浓度与前列腺癌发病率和死亡率的关联。对于前瞻性分析，使用多变量调整 Cox 回归对 199 698 名英国生物银行男性参与者进行风险评估。使用子样本的重复激素测量来校正回归稀释偏差的风险比 (HR)。对 IGF-I 和风险进行双样本孟德尔随机化 (MR) 分析，使用从英国生物银行男性中鉴定的遗传仪器和来自 PRACTICAL 联盟的遗传结果数据（79 148 例病例和 61 106 对照）。我们使用顺式和所有（顺式和反式）SNP MR 方法。共有 5402 名男性被诊断患有前列腺癌，其中 295 人死于前列腺癌（平均随访时间 6.9 年）。较高的循环 IGF-I 与前列腺癌诊断升高（每 5 nmol/L 增量的 HR = 1.09，95% CI 1.05-1.12）和死亡率（每 5 nmol/L 增量的 HR = 1.15，1.02-1.29）相关。 MR 分析还支持 IGF-I 在前列腺癌诊断中的作用（每 5 nmol/L 增量的顺式 MR 比值比 = 1.34, 1.07-1.68）。在观察分析中，较高的游离睾酮与较高的前列腺癌风险相关（每 50pmol/L 增量的 HR = 1.10, 1.05‐1.15）。较高的 SHBG 与较低的风险相关（每 10 nmol/L 增量的 HR = 0.95, 0.94‐0.97），两者都与前列腺癌死亡率无关。总睾酮水平与前列腺癌无关。这些发现表明 IGF-I 和游离睾酮与前列腺癌的发生和/或进展有关。 什么是新的？ 睾酮、胰岛素样生长因子-I (IGF-I) 和性激素结合球蛋白 (SHBG) 均与前列腺癌风险相关。在这项大型前瞻性研究中，作者分析了这些循环激素如何影响死亡率和风险。他们发现，IGF-I 较高的男性患前列腺癌和死亡的风险较高。游离睾酮水平较高的男性患前列腺癌的风险较高，而性激素结合球蛋白水平较高的男性患前列腺癌的风险较低。这些结果支持 IGF-I 和睾酮在前列腺癌发展中的作用。
Insulin‐like growth factor‐I (IGF‐I) and testosterone have been implicated in prostate cancer aetiology. Using data from a large prospective full‐cohort with standardised assays and repeat blood measurements, and genetic data from an international consortium, we investigated the associations of circulating IGF‐I, sex hormone‐binding globulin (SHBG), and total and calculated free testosterone concentrations with prostate cancer incidence and mortality. For prospective analyses, risk was estimated using multivariable‐adjusted Cox regression in 199 698 male UK Biobank participants. Hazard ratios (HRs) were corrected for regression dilution bias using repeat hormone measurements from a subsample. Two‐sample Mendelian randomisation (MR) analysis of IGF‐I and risk used genetic instruments identified from UK Biobank men and genetic outcome data from the PRACTICAL consortium (79 148 cases and 61 106 controls). We used cis‐ and all (cis and trans) SNP MR approaches. A total of 5402 men were diagnosed with and 295 died from prostate cancer (mean follow‐up 6.9 years). Higher circulating IGF‐I was associated with elevated prostate cancer diagnosis (HR per 5 nmol/L increment = 1.09, 95% CI 1.05‐1.12) and mortality (HR per 5 nmol/L increment = 1.15, 1.02‐1.29). MR analyses also supported the role of IGF‐I in prostate cancer diagnosis (cis‐MR odds ratio per 5 nmol/L increment = 1.34, 1.07‐1.68). In observational analyses, higher free testosterone was associated with a higher risk of prostate cancer (HR per 50 pmol/L increment = 1.10, 1.05‐1.15). Higher SHBG was associated with a lower risk (HR per 10 nmol/L increment = 0.95, 0.94‐0.97), neither was associated with prostate cancer mortality. Total testosterone was not associated with prostate cancer. These findings implicate IGF‐I and free testosterone in prostate cancer development and/or progression. What's new? Testosterone, insulin‐like growth factor‐I (IGF‐I), and sex hormone‐binding globulin (SHBG) all have been associated with prostate‐cancer risk. In this large, prospective study, the authors analyzed how these circulating hormones might impact mortality as well as risk. They found that men with higher IGF‐I had a higher risk of both prostate‐cancer diagnosis and mortality. Men with higher free testosterone had an increased risk of prostate cancer, while men with higher SHBG had a decreased risk. These results support the roles of IGF‐I and testosterone in prostate cancer development.
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影响因子：
5
作者：
Fry A;Littlejohns TJ;Sudlow C;Doherty N;Adamska L;Sprosen T;Collins R;Allen NE
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