Cancer Epidemiology Cohort in Male Health Professionals

项目总结/摘要 前列腺癌是美国最常见的癌症，也是癌症死亡的第二大常见原因。 男人据估计，到2030年，美国有超过300万男性患有前列腺癌。 患病率为560万前列腺癌幸存者补充剂使用的普遍性，通常是大剂量的， 在前列腺癌幸存者中尤其高，估计范围为20%至60%。虽然有益 效果尚未确定，有证据表明，诊断前摄入某些微量营养素， 高剂量可能会增加患前列腺癌的风险。因此，数百万患有前列腺癌的男性 目前正在服用高剂量的多种补充剂，尽管疗效的证据很少， 甚至有害，至少根据诊断前摄入的证据。我们提出了一个成本效益的研究， 利用卫生专业人员中5,500名前列腺癌幸存者的子队列的现有资源， 随访研究。每两年更新一次生活方式、饮食、前列腺癌治疗、PSA水平、 临床进展和30年内收集的合并症，将使我们能够检查长期- 术语效应（持续时间，潜伏期），来源（天然与合成）和剂量，并确定形状 任何非线性剂量反应关系。我们将重点介绍常见的膳食补充剂， 前列腺癌幸存者，也因其与前列腺癌的关联而被广泛研究 发病率，但缺乏生存数据，即，钙，视黄醇（维生素A），硒，维生素E，锌，和海洋 ω-3脂肪酸首先，我们将测试是否独立于诊断前摄入，诊断后 补充钙、视黄醇、锌、硒、维生素E和ω-3脂肪酸的摄入量 特征为与致死性前列腺癌呈J形或U形剂量反应关系， 在较低剂量下，相关或反向相关，在较高剂量下，死亡率增加（目标1）。 其次，我们将评估诊断后更长时间的高剂量补充剂摄入是否 与前列腺癌幸存者中致死性前列腺癌的高风险相关（目的2）。考虑 膳食补充剂的广泛使用，以及大量且不断增加的前列腺癌幸存者， 据估计，2030年的患病率为560万，即使是饮食之间的微小或适度关联， 补充剂和前列腺癌预后将具有重大的临床和公共卫生影响。

Project Summary/Abstract Prostate cancer is the most common cancer and the second most common cause of cancer death in U.S. men. Over 3 million men are currently living with prostate cancer in the U.S. By 2030, the estimated prevalence is 5.6 million prostate cancer survivors. Prevalence of supplement use, often in mega-doses, is particularly high in prostate cancer survivors with estimates ranging from 20% to 60%. Although beneficial effects are not established, evidence suggest that pre-diagnostic intake of certain micronutrients taken at high doses may increase risk of developing prostate cancer. Thus, millions of men with prostate cancer are currently taking high doses of numerous supplements, despite minimal evidence of efficacy, and possibly even harm, at least based on evidence from pre-diagnostic intake. We propose a cost-efficient study, utilizing existing resources from a sub-cohort of 5,500 prostate cancer survivors in the Health Professionals Follow-up Study. Biennially updated detailed data on lifestyle, diet, prostate cancer treatments, PSA levels, clinical progression, and co-morbidities collected over a period of 30 years, will allow us to examine long- term effects (duration, latency), source (natural versus synthetic), and dose, and to determine the shape of any non-linear dose-response relationship. We will focus on dietary supplements commonly used by prostate cancer survivors, which have also been widely studied for their association with prostate cancer incidence, but lack data for survival, i.e., calcium, retinol (vitamin A), selenium, vitamin E, zinc, and marine omega-3 fatty acids. First, we will test whether independent of pre-diagnostic intake, post-diagnostic intakes of supplemental calcium, retinol, zinc, selenium, vitamin E, and omega-3 fatty acid are characterized by a J-shaped or U-shaped dose-response relationship with lethal prostate cancer, with no association or inverse associations at lower doses, and increased mortality at higher doses (Aim 1). Second, we will assess whether longer post-diagnostic duration of high-dose supplement intake is associated with higher risk of lethal prostate cancer in prostate cancer survivors (Aim 2). Considering the widespread use of dietary supplements, and the large and increasing number of prostate cancer survivors, with an estimated prevalence of 5.6 million in 2030, even a small or modest association between dietary supplements and prostate cancer prognosis will have substantial clinical and public health impact.