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

肥胖是全球公共健康问题，三分之二的美国男性超重或肥胖。对于前列腺癌患者来说，肥胖的流行令人担忧，因为在确诊前或确诊时超重的男性，其生化复发和癌症特有死亡率的风险会增加。肥胖和致命的前列腺癌之间的联系存在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的翻译潜力。 我们的研究旨在阐明肥胖和致命性前列腺癌之间联系的潜在机制，并确定更容易受到肥胖环境影响的患者亚群。我们假设肥胖可能通过局部肿瘤效应起作用。 通过局部肿瘤效应来增加前列腺癌的致命性，以及通过 为转移性生长的“土壤”提供燃料的系统效应。我们专注于新陈代谢和炎症 途径--两个与肥胖有关的区域--以及研究前列腺癌局部虹膜的生物标志物 组织和循环中也是如此。此外，我们在肿瘤中采用了基于发现的目标来识别新的 前列腺癌患者超重并发展为致命癌症的肿瘤中丰富的通路， 这一努力可能会为二级预防带来新的机会。我们以人口为基础的研究 肥胖和致命性前列腺癌在参与研究的前列腺癌患者中嵌套 在前列腺癌生物库中的DF/HCG孢子内，为其提供前列腺组织和血液标本 都是可用的，并且唯一地专注于致命的癌症作为主要终点。 肥胖是发现致命性前列腺癌诱因的一种手段，也是一种可改变的风险。 二级预防中的因素。减肥是具有挑战性的，因此识别肿瘤的特定途径 在循环中，肥胖与致命的前列腺癌联系的最重要的基础是关键信息 最佳预防策略。该项目的翻译目标是识别高血压病患者 肥胖后果的风险，以便为随机试验的设计提供信息，并增加 二级预防策略的成功。这项工作将使我们详细了解 致命性前列腺癌中肥胖的前列腺和全身驱动因素，这一努力将加强因果关系 协会的成员。

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.