Effects of Exercise on Visceral Adiposity & Hyperinsulinemia in Colon Cancer Survivor

描述(由申请人提供)：高复发率是促进结肠癌(CC)幸存者健康和长寿的关键障碍。减少这一障碍的一种方法是开发干预措施，将CC幸存者可以自主完成的复发降至最低，例如生活方式和行为改变。观察流行病学数据表明，确诊为CC后的体力活动可将癌症复发风险降低40%，CC特有死亡率降低45%-71%，全因死亡率降低57%-63%。然而，这种联系的潜在生物学途径仍未确定。过多的内脏脂肪组织(VAT)和高胰岛素血症在CC幸存者的复发和转移性疾病的发展中起着关键作用。VAT是CC幸存者的无病生存率、CC特异性死亡率和全因死亡率的独立预测因子。VAT在代谢上是活跃的，并导致高胰岛素血症的发生。胰岛素刺激CC细胞的生长和增殖，作为催化剂促进复发和转移性疾病的发生和发展。降低VAT和胰岛素可能有利于改变发生复发和转移性疾病的风险，提高CC患者的生存质量和寿命。有氧运动以剂量-反应方式降低非糖尿病肥胖者的增值税和胰岛素。然而，在CC幸存者中，运动对VAT和胰岛素的剂量-反应效应还没有具体的特征。为了解决这一认识差距，我们将利用第二阶段随机、为期六个月的剂量-反应运动试验的开始(勇气试验；R21CA182767)，在39名CC幸存者中，将150min�wk-1或300min�wk-1中等强度有氧运动与等待名单对照组进行比较。我们将利用这项试验，增加一种创新的、最近得到验证的基于双能X射线吸收法的方法来量化增值税，并使用现有的血液样本来量化空腹胰岛素。本试验的主要目的是量化和描述中等强度有氧运动对VAT和空腹胰岛素的剂量反应效应。我们将探讨增值税改善与空腹胰岛素改善之间的相关性。为CORAGE试验配备这些测量提供了一个独特的机会，可以收集关于运动对生物标记物(如VAT和胰岛素)的剂量反应效应的补充知识，这些生物标记物与CC结果有关。这项研究经验与一套具有交叉主题的教学课程相结合，其中包括癌症流行病学、护理学和癌症生物学。这项研究的目的与NCI的挑衅性问题PQA-2一致，PQA-2试图阐明不同剂量的运动如何影响癌症预后和预后生物标记物。

DESCRIPTION (provided by applicant): The high rate of recurrent disease is a critical barrier to promote the health and longevity of colon cancer (CC) survivors. An approach to reduce this barrier is to develop interventions to minimize recurrence that CC survivors can accomplish autonomously, such as lifestyle and behavioral modification. Observational epidemiologic data suggest physical activity after diagnosis of CC reduces the risk of cancer recurrence by 40%, CC-specific mortality by 45-71%, and all-cause mortality by 57-63%. However, the underlying biological pathway of this association remains uncharacterized. Excess visceral adipose tissue (VAT) and hyperinsulinemia play a pivotal role in the development of recurrent and metastatic disease among CC survivors. VAT is an independent predictor of disease-free survival, CC-specific mortality, and all-cause mortality among CC survivors. VAT is metabolically active and lends rise to the development of hyperinsulinemia. Insulin stimulates the growth and proliferation of CC cells, acting as a catalyst to promote the initiation and progression of recurrent and metastatic disease. Reducing VAT and insulin may favorably alter the risk of developing recurrent and metastatic disease, and improve the quality and longevity of CC survivorship. Aerobic exercise reduces VAT and insulin in dose-response fashion among non-diabetic persons with obesity. However, the dose-response effects of exercise on VAT and insulin have not been characterized specifically among CC survivors. To address this knowledge gap, we will leverage the commencement of a phase II, randomized, six-month, dose-response exercise trial (The COURAGE Trial; R21 CA182767) that will compare 150 min�wk-1 or 300 min�wk-1 of moderate-intensity aerobic exercise to a wait-list control group among 39 CC survivors. We will harness this trial by adding an innovative and recently-validated dual energy x-ray absorptiometry-based methodology to quantify VAT, and use existing blood samples to quantify fasting insulin. The primary aims of this trial are to quantify and describe the dose response effects of moderate-intensity aerobic exercise on VAT and fasting insulin. We will explore the correlation between improvements in VAT and improvements in fasting insulin. Equipping the COURAGE trial with these measurements provides a unique opportunity to glean complementary knowledge about the dose-response effects of exercise on biomarkers, such as VAT and insulin, which are implicated in CC outcomes. This research experience is coupled with a set of didactic courses with cross-cutting themes that include cancer epidemiology, nursing science, and cancer biology. The aims of this research are consistent with NCI provocative question PQA-2, which seeks to elucidate how varying doses of exercise influence cancer prognosis and prognostic biomarkers.