Effect of Aerobic Exercise on Genomic Signatures of Prostate Cancer Prognosis

有氧运动对前列腺癌预后基因组特征的影响

• 批准号: 8615849
• 负责人: JUNE ML CHAN
• 金额: $ 66.28万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-14 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8615849
• 关键词: Address; Adherence; Adoption; Adverse effects; Aerobic Exercise; Affect; Anxiety; Base Excision Repairs; Biological; Biology; Biopsy; California; Cancer Biology; Cancer Prognosis; Cancer Survivor; Cessation of life; Clinical; Comorbidity; Control Groups; DNA Repair; DNA Repair Pathway; Data; Development; Diagnosis; Disease; Disease Progression; Erectile dysfunction; Exercise; Future; Gene Expression; Genomics; Gleason Grade for Prostate Cancer; Goals; Grant; Growth Factor; Home environment; Human; Incontinence; Indolent; Lead; Longitudinal Studies; Malignant Neoplasms; Malignant neoplasm of prostate; Messenger RNA; Mitogen-Activated Protein Kinase 14; Mus; Neoplasm Metastasis; Normal tissue morphology; Outcome; Pathologic; Pathway interactions; Pattern; Phase III Clinical Trials; Phenotype; Phosphatidylinositols; Phosphotransferases; Physical activity; Plasma; Probability; Prognostic Marker; Prostate; Prostate Cancer therapy; Prostate-Specific Antigen; Prostatic Neoplasms; Protocols documentation; Public Health; RNA; Radiosurgery; Randomized Controlled Trials; Recommendation; Reporting; Research; Risk; San Francisco; Signal Pathway; Signal Transduction; Staging; Stress; Testing; Time; Tissues; Toxic effect; Tumor Tissue; United States; Universities; Vascular Endothelial Growth Factors; Vascularization; Walking; Work; adverse outcome; angiogenesis; arm; base; cancer diagnosis; cohort; disorder risk; fitness; follow-up; high risk; improved; lifestyle intervention; mRNA Expression; men; novel; post intervention; programs; psychosocial; public health priorities; public health relevance; treatment as usual; tumor; tumor progression

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.

标题：有氧运动对前列腺癌预后基因组特征的影响： 7。项目摘要/摘要： 前列腺癌是美国男性中最常见的癌症 2012年有241,000个新诊断。近一半被诊断出患有早期，低度疾病，并且 可能是主动监视的好候选者（AS）。这是一个重要的管理选项，因为它 减少过度治疗，包括标准的严重副作用（例如尿失禁，勃起功能障碍） 前列腺癌疗法。但是，由于目前的临床测试是不完美的，因此 敏锐的侵略性前列腺癌。此外，最初约有15％ 由于焦虑和 知道自己患有癌症的压力。因此，确定降低前列腺癌风险的策略 进展和缓解特异性焦虑可能会大大减少低风险前列腺癌的过度治疗 并受益于公共卫生。我们报道了前列腺癌后剧烈的体育锻炼和轻快的行走 诊断与两个不同的队列中前列腺癌进展或死亡的降低有关 患有前列腺癌的男性。在引人注目的同时，这些研究无法解决是否增加有氧运动之后 诊断有利地改变了前列腺癌的生物学。我们的小组和其他人已经确定和验证了小说 前列腺基因组特征预测患有低风险前列腺癌的男性临床结果不良，并且 证明前列腺中的基因表达是通过短期生活方式干预来改变的。因此，我们 建议进行一项随机对照试验，以评估是否有24周的有氧有氧运动 练习与通常的护理会影响120名男性中三个经过验证的前列腺基因组特征的表达 在加利福尼亚大学，旧金山和杜克大学接受前列腺癌。分配的男人 到运动臂将参加一个单独量身定制的跑步机，其中包括五个30- 每周45分钟的课程，占基线心肺健身的50-80％（三个监督，在家中有两个）。 我们还将检查有氧运动对癌症相关途径mRNA表达的全球影响 肿瘤和正常组织（例如生长因子信号传导，血管生成，DNA修复）；以及有氧运动 与通常的护理相比，运动减轻了与焦虑和总体压力。常规协议 前列腺活检提供了一个独特的机会，可以研究有氧运动对 前列腺癌生物学。这项随机对照试验的结果将提供基本证据 需要支持运动和前列腺癌进展的确定性III期临床试验。