Effect of Aerobic Exercise on Genomic Signatures of Prostate Cancer Prognosis

标题：有氧运动对前列腺癌预后基因组特征的影响： 7.项目总结/摘要： 前列腺癌是美国男性中最常见的癌症， 2012年新诊断241，000例。近一半的男性诊断为早期，低度疾病， 可能是主动监视（AS）的良好候选人。AS是一个重要的管理选项，因为它 减少过度治疗，包括严重的副作用（例如，失禁，勃起功能障碍）的标准 前列腺癌的治疗然而，由于目前的临床试验不完善， 区分惰性和侵袭性前列腺癌。此外，大约15%的男性最初 选择AS最终在没有生物进展的情况下寻求治愈性治疗，由于焦虑和 知道自己得了癌症的压力因此，确定降低前列腺癌风险的策略 进展和减轻AS特异性焦虑可以大大减少低风险前列腺癌的过度治疗 有益于公众健康。我们报告说，前列腺癌后剧烈的体力活动和快走 在两个不同的队列中，诊断与前列腺癌进展或死亡减少约60%相关 前列腺癌的患者。虽然令人信服，但这些研究并没有解决在运动后增加有氧运动的问题。 诊断有利地改变前列腺癌生物学。我们的团队和其他人已经确定并验证了新的 预测低风险前列腺癌男性临床结局较差的前列腺基因组特征，以及 研究表明，前列腺中的基因表达通过短期生活方式干预而改变。因此我们 我建议进行一项随机对照试验，以评估是否24周的监督有氧运动 运动与常规护理影响120名男性中三种经验证的前列腺基因组特征的表达 在加州大学、弗朗西斯科大学和杜克大学，分配的男子 到锻炼手臂将参加一个单独定制的跑步机步行计划，其中包括五个30- 每周45分钟的训练，心肺功能达到基线的50-80%（三次监督，两次在家）。 我们还将研究有氧运动对癌症相关通路mRNA表达的整体影响， 肿瘤和正常组织（例如生长因子信号传导、血管生成、DNA修复）;以及是否需氧 与常规护理相比，运动减少了AS相关的焦虑和整体压力。规则的AS协议 前列腺活检提供了一个独特的机会来研究有氧运动对前列腺的纵向影响。 前列腺癌生物学这项随机对照试验的结果将提供必要的证据， 需要支持一项关于运动和前列腺癌进展的确定性III期临床试验。

Title: Effect of Aerobic Exercise on Genomic Signatures of Prostate Cancer Prognosis: 7. PROJECT SUMMARY/ABSTRACT: Prostate cancer is the most commonly diagnosed cancer among men in the United States with more than 241,000 new diagnoses in 2012. Nearly half of the men diagnosed have early stage, low-grade disease, and may be good candidates for active surveillance (AS). AS is an important management option because it reduces overtreatment, including the serious side effects (e.g., incontinence, erectile dysfunction) of standard prostate cancer therapies. However, AS is under-utilized because current clinical tests are imperfect at discerning indolent from aggressive prostate cancer. Furthermore, approximately 15% of men who initially opt for AS ultimately seek curative treatment in the absence of biological progression, due to the anxiety and stress of knowing they have cancer. Hence, identifying strategies that reduce risk of prostate cancer progression and allay AS-specific anxiety could greatly reduce the overtreatment of low risk prostate cancer and benefit public health. We reported that vigorous physical activity and brisk walking after prostate cancer diagnosis were associated with ~60% reductions in prostate cancer progression or death in two distinct cohorts of men with prostate cancer. While compelling, these studies do not address if increasing aerobic exercise after diagnosis favorably alters prostate cancer biology. Our group and others have identified and validated novel prostate genomic signatures that predict poor clinical outcomes among men with low risk prostate cancer, and demonstrated that gene expression in the prostate is modified by short-term lifestyle interventions. Thus, we propose to conduct a randomized controlled trial to evaluate whether 24 weeks of supervised aerobic exercise vs. usual care affects the expression of three validated prostate genomic signatures among 120 men with prostate cancer on AS at the University of California, San Francisco and Duke University. Men assigned to the exercise arm will participate in an individually tailored treadmill-walking program that includes five 30- 45 minute sessions per week at 50-80% of baseline cardiorespiratory fitness (three supervised, two at home). We will also examine the global effects of aerobic exercise on mRNA expression of cancer-related pathways in tumor and normal tissue (e.g. growth factor signaling, angiogenesis, DNA repair); and whether aerobic exercise reduces AS-related anxiety and overall stress compared to usual care. The AS protocol of regular prostate biopsies provides a unique opportunity to study the longitudinal effects of aerobic exercise on prostate cancer biology. The results of this randomized controlled trial will provide the essential evidence needed to support a definitive phase III clinical trial of exercise and prostate cancer progression.