Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Unit of Health-Care Epidemiology, Big Data Institute, NIHR Oxford Biomedical Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Int J Cancer. 2020 Aug 1;147(3):803-810. doi: 10.1002/ijc.32808. Epub 2019 Dec 11.
Insulin-like growth factor-I (IGF-I) and testosterone may be related to prostate cancer risk. Acromegaly is associated with clinically high IGF-I concentrations. Klinefelter's syndrome, testicular hypofunction and hypopituitarism are associated with clinically low testosterone concentrations. We aimed to investigate whether diagnosis with these conditions was associated with subsequent prostate cancer diagnosis and mortality. We used linked English national Hospital Episode Statistics and mortality data from 1999 to 2017 to construct and follow-up cohorts of men aged ≥35 years diagnosed with (i) acromegaly (n = 2,495) and (ii) hypogonadal-associated diseases (n = 18,763): Klinefelter's syndrome (n = 1,992), testicular hypofunction (n = 8,086) and hypopituitarism (n = 10,331). We estimated adjusted hazard ratios (HRs) and confidence intervals (CIs) for prostate cancer diagnosis and death using Cox regression in comparison with an unexposed reference cohort of 4.3 million men, who were admitted to hospital for a range of minor surgeries and conditions (n observed cases = 130,000, n prostate cancer deaths = 30,000). For men diagnosed with acromegaly, HR for prostate cancer diagnosis was 1.33 (95% CI 1.09-1.63; p = 0.005; n observed cases = 96), HR for prostate cancer death was 1.44 (95% CI 0.92-2.26; p = 0.11; n deaths = 19). Diagnosis with Klinefelter's syndrome was associated with a lower prostate cancer risk (HR = 0.58, 95% CI 0.37-0.91; p = 0.02; n observed cases = 19) and hypopituitarism was associated with a reduction in prostate cancer death (HR = 0.53, 95% CI 0.35-0.79; p = 0.002; n deaths = 23). These results support the hypothesised roles of IGF-I and testosterone in prostate cancer development and/or progression. These findings are important because they provide insight into prostate cancer aetiology.
胰岛素样生长因子-I（IGF-I）和睾酮可能与前列腺癌风险有关。肢端肥大症与临床高 IGF-I 浓度有关。克氏综合征、睾丸功能减退和垂体功能减退与临床低睾酮浓度有关。我们旨在研究这些疾病的诊断是否与随后的前列腺癌诊断和死亡率相关。我们使用 1999 年至 2017 年英国国家医院发病统计数据和死亡率数据，构建并随访年龄≥35 岁的男性队列：肢端肥大症（n=2495）和（ii）与性腺功能减退相关的疾病（n=18763）：克氏综合征（n=1992）、睾丸功能减退（n=8086）和垂体功能减退（n=10331）。我们使用 Cox 回归估计了前列腺癌诊断和死亡的调整后的危险比（HR）和置信区间（CI），并与 430 万男性的未暴露参考队列进行了比较，这些男性因各种小手术和疾病住院（观察到的病例数=130000，前列腺癌死亡人数=30000）。对于诊断为肢端肥大症的男性，前列腺癌诊断的 HR 为 1.33（95%CI 1.09-1.63；p=0.005；观察到的病例数=96），前列腺癌死亡的 HR 为 1.44（95%CI 0.92-2.26；p=0.11；死亡人数=19）。克氏综合征的诊断与较低的前列腺癌风险相关（HR=0.58，95%CI 0.37-0.91；p=0.02；观察到的病例数=19），垂体功能减退与前列腺癌死亡减少相关（HR=0.53，95%CI 0.35-0.79；p=0.002；死亡人数=23）。这些结果支持 IGF-I 和睾酮在前列腺癌发展和/或进展中的假设作用。这些发现很重要，因为它们提供了对前列腺癌病因的深入了解。
