Energy Balance-Related Hormones & Prostate Cancer Incidence & Progression

摘要 最近的证据证实，正能量平衡，如肥胖估计，强烈影响 前列腺癌然而，能量平衡如何影响和被影响的复杂性， 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，能量平衡的影响对于前列腺可能不同。 癌症发病率和进展。第三个复杂的因素是，早期- 初发和晚发前列腺癌。根据初步数据，我们提出了三种不同的模式 以及其他研究，其中能量平衡相关变量影响前列腺癌： 模式1：与肥胖和缺乏体力活动相关的代谢改变，包括高胰岛素和低血糖。 瘦素和低脂联素水平增加前列腺癌进展风险。此外，低睾丸激素 与肥胖相关的水平可能会导致更多的低分化癌症， 预后 模式2：较高的胰岛素样生长因子（IGF-1）水平影响良好至中度良好的进展 分化的前列腺癌，而在IGF-1信号传导中具有分子改变的癌症 因此，IGF-1信号通路的上调对循环IGF-1水平相对不敏感。 模式3：具有与SNS活动相关的固有代谢表型的年轻男性， 从体重增加中摄取能量，并与慢性前列腺炎/慢性骨盆疼痛综合征有关 前列腺炎是在前列腺癌的风险增加。 我们将讨论这三种模式，即能量平衡可能会影响前列腺癌的风险，在健康 专业人士随访研究（HPFS），一个队列的47,000名男性在1986年基线无癌症。我们 到2010年，预计将有6,085例新的前列腺癌病例，其中包括668例死亡病例，肿瘤块超过 1，900例直肠切除术。HPFS中暴露数据的来源为问卷调查，包括饮食， 人体测量、活动、药物使用和血浆样本。结局数据将基于 (1)医疗记录和病理报告审查，以及（2）与疾病相关的组织块标记 进展分层分析和多变量分析将用于控制混杂因素。我们 最终目标是更好地了解体重，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.