Energy Balance-Related Hormones & Prostate Cancer Incidence & Progression

摘要 最近的证据证实，根据肥胖的估计，正能量平衡对 前列腺癌的发生。然而，能量平衡如何影响并受其影响的复杂性 各种代谢激素和交感神经系统活动(SNS)增加了相当大的复杂性 能量平衡在癌症中的作用。此外，能量平衡对前列腺的影响可能有所不同。 癌症的发病率和进展。第三个复杂的因素是，可能有不同的病因导致早期- 首发和晚发前列腺癌。根据我们的初步数据，我们提出了三种不同的模式 以及其他与能量平衡相关的变量影响前列腺癌的研究： 模式1：与肥胖和缺乏体力活动相关的代谢变化，包括高胰岛素和 瘦素和低水平的脂联素会增加前列腺癌进展的风险。此外，睾丸激素水平较低 与肥胖相关的水平可能会导致更低分化的癌症，从而导致更糟糕的 预后。 模式2：较高的胰岛素样生长因子(IGF-1)水平影响健康到中等健康的进展 分化前列腺癌，而IGF-1信号分子改变的癌症 因此，上调的IGF-1信号对循环中的IGF-1水平相对没有反应。 模式3：具有与SNS活动相关的固有代谢表型的年轻男性 体重增加引起的能量摄入与慢性前列腺炎/慢性盆腔疼痛综合征相关 前列腺炎患前列腺癌的风险增加。 我们将解决这三种能量平衡可能影响健康中前列腺癌风险的模式 专业人士跟踪研究(HPFS)，一个队列的47,000名男性在基线上没有癌症在1986年。我们 计划到2010年新增前列腺癌病例6,085例，其中包括668例死亡病例，肿瘤块超过 前列腺摘除1900例。HPFS中暴露数据的来源是问卷，包括饮食、 人体测量、活动、用药和血浆样本。结果数据将基于 (1)病历和病理报告审查；(2)与疾病相关的组织块标志物 进步。采用分层分析和多元分析对混杂因素进行控制。我们的 最终目标是更好地了解体重以及相关的饮食和其他可改变的因素， 在不同阶段影响前列腺癌的发生。

Abstract Recent evidence has confirmed that positive energy balance, as estimated by obesity, strongly influences prostate carcinogenesis. However, the complexity of how energy balance influences, and is influenced, by various metabolic hormones and sympathetic nervous system activity (SNS) adds considerable complexity to the role of energy balance for this cancer. Further, the influences of energy balance may differ for prostate cancer incidence and progression. A third complicating factor is that there may be distinct etiologies for early- onset and late-onset prostate cancers. We propose three distinct patterns, suggested by our preliminary data and other studies, whereby energy balance related variables influence prostate cancer: Pattern 1: Metabolic alterations associated with obesity and lack of physical activity, including high insulin and leptin, and low adiponectin levels, increase risk of prostate cancer progression. Further, the low testosterone levels associated with obesity may contribute to more poorly differentiated cancers and thus a worse prognosis. Pattern 2: Higher insulin-like growth factor (IGF-1) levels influence progression of well- to moderately-well differentiated prostate cancers, whereas cancers that have molecular alterations in the IGF-1 signaling pathway and hence upregulated IGF-1 signaling are relatively unresponsive to circulating IGF-1 levels. Pattern 3: Younger men with an inherent metabolic phenotype related to SNS activity that disassociates high energy intake from weight gain and which is associated with chronic prostatitis/chronic pelvic pain syndrome prostatitis are at increased risk of prostate cancer. We will address these three patterns whereby energy balance may influence prostate cancer risk in the Health Professionals Follow-up Study (HPFS), a cohort of the 47,000 men free of cancer at baseline in 1986. We project 6,085 new cases of prostate cancer by 2010, including 668 fatal cases, with tumor blocks from over 1,900 prostatectomy cases. The sources of the exposure data in the HPFS are questionnaire, including diet, anthropometric measures, activity, medication use, and plasma samples. The outcome data will be based on (1) medical record and pathology report review, and (2) tissue block markers that correlate with disease progression. Stratified analysis and multivariate analysis will be used to control for confounding factors. Our ultimate goal is to better understand how body weight, and related dietary and other modifiable factors, influence prostate carginogenesis at various stages.