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

描述（由申请人提供）：疾病复发率高是促进结肠癌（CC）幸存者健康和长寿的关键障碍。减少这种障碍的一种方法是开发干预措施，以减少复发，CC幸存者可以自主完成，如生活方式和行为的改变。观察性流行病学资料显示，确诊为CC后进行体育锻炼可降低40%的癌症复发风险，可降低45-71%的CC特异性死亡率，可降低57-63%的全因死亡率。然而，这种关联的潜在生物学途径仍不清楚。过量内脏脂肪组织（VAT）和高胰岛素血症在CC幸存者复发和转移性疾病的发展中起关键作用。VAT是一个独立的无病生存、CC特异性死亡率和CC幸存者全因死亡率的预测因子。VAT代谢活跃，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，作为促进复发和转移性疾病的开始和进展的催化剂。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，并改善CC的生存质量和寿命。有氧运动在非糖尿病肥胖人群中以剂量-反应方式降低VAT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尚未被明确表征。为了解决这一知识差距，我们将利用一项II期、随机、为期6个月的剂量反应运动试验（COURAGE试验；R21 CA182767）的开始，将39名CC幸存者中150分钟/周或300分钟/周的中等强度有氧运动与等待列表对照组进行比较。我们将利用这项试验，增加一种创新的、最近验证的基于双能x射线吸收测量的方法来量化VAT，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VAT改善与空腹胰岛素改善之间的相关性。为COURAGE试验配备这些测量提供了一个独特的机会，可以收集有关运动对生物标志物（如VAT和胰岛素）的剂量反应效应的补充知识，这些生物标志物与CC结果有关。这一研究经验与一系列交叉主题的教学课程相结合，包括癌症流行病学，护理科学和癌症生物学。本研究的目的与NCI的争议性问题PQA-2一致，该问题旨在阐明不同剂量的运动如何影响癌症预后和预后生物标志物。

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.