Tumor and Circulating Markers as Links Between Obesity and Lethal Prostate Cance

肥胖是一个全球性的公共卫生问题，三分之二的美国男性超重或肥胖。对于前列腺癌患者，肥胖流行是令人担忧的，因为在诊断之前或诊断时超重的男性的生化复发和癌症特异性死亡率的风险增加。肥胖和致命性前列腺癌之间的关联有几个悬而未决的问题，需要这些问题的答案来阐明前列腺癌患者中的转化潜力。 我们的研究旨在阐明肥胖和致死性前列腺癌之间联系的潜在机制，并确定更易受肥胖环境影响的患者亚组。我们假设肥胖可能通过局部肿瘤效应起作用， 通过局部肿瘤效应，这是增加前列腺癌致命潜力的“种子”，以及通过 系统性影响，为转移性生长提供“土壤”。我们专注于新陈代谢和炎症 途径--两个与肥胖有联系的领域--并研究前列腺局部的生物标志物IRI 组织和循环中。此外，我们在肿瘤中采用基于发现的目的来识别新的 在超重并发展成致命癌症的前列腺癌患者的肿瘤中富集的途径， 并奋进为二级预防提供新的机会。我们的基于人群的研究 肥胖和致命的前列腺癌嵌套在参与者中患有前列腺癌的男性中 在前列腺癌生物储存库中的DF/HCG孢子内， 是可用的，并且独特地专注于致命癌症作为主要终点。 肥胖是发现致命前列腺癌驱动因素的一种手段，也是一种可改变的风险 二级预防的因素。减肥具有挑战性，因此要确定肿瘤中的特定途径 在循环中，肥胖与致命的前列腺癌之间的联系是至关重要的， 最佳预防策略。该项目的翻译目标是识别高血压患者， 肥胖后果的风险，以便为随机试验的设计提供信息， 二级预防战略的成功。这项工作将导致详细了解的影响， 前列腺和全身肥胖的驱动因素对致命的前列腺癌，一项奋进，将加强因果关系 协会的。

Obesity is a public health problem globally, and two-thirds of US men are overweight or obese. For prostate cancer patients, the obesity epidemic is of concern since men who are overweight before or at the time of diagnosis are at increased risk of biochemical recurrence and cancer-specific mortality. There are several outstanding questions underlying the association between obesity and lethal prostate cancer whose answers are needed to shed light on the translational potential among prostate cancer patients. Our study aims to elucidate mechanisms underlying the link between obesity and lethal prostate cancer and identify patient subgroups more susceptible to the obesity milieu. We hypothesize that obesity may act through local tumor effects which are We hypothesize that obesity may act through local tumor effects which are "the seed" to increase a prostate cancer's lethal potential as well as via systemic effects that fuel "the soil" for metastatic growrth. We focus on metabolism and inflammation pathways - two domains with established links to obesity—and investigate biomarkers iri locally in prostate tissue as well as in circulation. Moreover, we employ a discovery-based aim in tumors to identify novel pathways enriched in the tumors of prostate cancer patients who are overweight and develop lethal cancer, and endeavor that may unveil new opportunities for secondary prevention. Our population-based study of obesity and lethal prostate cancer is nested among men with incident prostate cancer who were participants within the DF/HCG SPORE in Prostate Gancer biorepository for whom prostate tissue and blood specimens are available, and uniquely focuses on lethal cancer as the primary endpoint. Obesity represents a means to discover drivers of lethal prostate cancer, as well as being a modifiable risk factor in secondary prevention. Weight loss is challenging, and thus identifying specific pathways in tumors and in circulation most strongly underlying the obesity-lethal prostate cancer link is critical to inform on optimal prevention strategies. The translational goals ofthe project are the identification of patients at high risk of the consequences of obesity in order to inform the design of randomized trials and augment the success of secondary prevention strategies. The work will lead to a detailed understanding of the effect of prostatic and systemic drivers of obesity on lethal prostate cancer, an endeavor that will strengthen causality of the association.