Body Composition, Weight, and Colon Cancer Survival

描述（申请人提供）：流行病学和科学研究表明，肥胖对患结直肠癌的风险有显著影响。然而，肥胖与结直肠癌（CRC）预后之间的关系不太令人信服。虽然一些研究发现严重肥胖患者（BMI为e35 kg/m2）复发和/或死亡的风险增加，但大多数研究发现诊断后体重指数（BMI）或体重增加与结直肠癌预后之间没有关联。BMI和结直肠癌终点之间缺乏一致的研究结果，部分原因可能是BMI在疾病背景下可能不能很好地替代身体成分。脂肪组织和肌肉质量对体内的内分泌、免疫和激素产生强大但不同的影响。虽然超重的人往往有较高的瘦肉和脂肪量，但超重或肥胖的人可能存在低水平的肌肉量；即使在脂肪增加的情况下，肌肉减少症（肌肉萎缩）在癌症幸存者中也很常见。因此，我们建议使用收集的腹部CT扫描作为诊断时和诊断后1-2年的常规分期和监测的一部分，以评估2005年至2010年期间在Kaiser Permanente Northern California （KPNC）诊断为I-III期侵袭性结直肠癌（CRC）的人群（n=3546）的脂肪和肌肉质量，并检查身体组成与CRC生存的关系。具体来说，我们将检查CRC幸存者在诊断时的肌肉萎缩（肌肉减少症）和过量脂肪量（FM）水平（目的1），FM和诊断时肌肉量与CRC生存之间的关系（目的2），FM和肌肉量在诊断和诊断后1至2年之间的变化是否随诊断后体重变化而变化（目的3）。以及在诊断期间和诊断后1至2年测量的FM和肌肉质量的变化是否与CRC生存相关（Aim 4）。这项研究使用了一种新颖的、最先进的工具来收集比身高和体重标准测量更准确的身体成分测量，并可以为能量平衡和身体成分在癌症生存中的作用提供重要的见解。这项研究将有助于识别肌肉萎缩高风险的CRC患者，并可能提高我们对为什么BMI与CRC事件相关而与CRC结局无关的理解。使用CT扫描来评估脂肪/肌肉质量可以很容易地在临床或流行病学环境中完成，为BMI增加了一个重要的生理指标，以帮助制定和个性化体重控制策略和其他治疗方法，以防止肌肉质量损失，潜在地提高生存率。因此，这项研究的发现可能会导致临床实践的改变。此外，关于脂肪/肌肉作用的见解

DESCRIPTION (provided by applicant): Epidemiologic and scientific research shows that obesity has a significant influence on the risk of developing colorectal cancer. However, associations between adiposity and colorectal cancer (CRC) prognosis are less convincing. While some studies have found severely obese patients (BMI, e35 kg/m2) to have an increased risk of recurrence and/or death, most studies have found no association between body mass index (BMI) or weight gain after diagnosis and CRC prognosis. The lack of consistent findings between BMI and colorectal cancer endpoints may be due in part to the fact that BMI may be a poor surrogate for body composition in the context of illness. Adipose tissue and muscle mass exert powerful but different endocrine, immune, and hormonal influences within the body. Though overweight persons tend to have both higher amounts of lean and fat mass, low levels of muscle mass may be present in overweight or obese people; sarcopenia (muscle wasting) is common among cancer survivors, even in the presence of fat gain. Therefore, we propose to use abdominal CT scans collected as part of routine staging and surveillance both at diagnosis and 1-2 years after diagnosis, to assess fat and muscle mass and to examine the relationship of body composition to CRC survival in a cohort of persons (n=3546) diagnosed between 2005 and 2010 with Stage I-III invasive colorectal cancer (CRC) at Kaiser Permanente Northern California (KPNC). Specifically, we will examine the level of muscle wasting (sarcopenia) and excess fat mass (FM) in CRC survivors at diagnosis (Aim 1), the association between FM and muscle mass at diagnosis and CRC survival (Aim 2), whether changes in FM and muscle mass measured between diagnosis and 1 to 2 years after diagnosis vary by weight change post-diagnosis (Aim 3), and whether changes in FM and muscle mass measured between diagnosis and 1 to 2 years after diagnosis are associated with CRC survival (Aim 4). This study uses a novel, state-of-the art tool to collect more accurate measures of body composition than standard measures of height and weight, and could provide important insight into the role of energy balance and body composition in cancer survival. This study will enable identification of CRC patients who are at high risk for muscle wasting and may improve our understanding of why BMI is related to incident CRC but not CRC outcomes. The use of CT scans to assess fat/muscle mass could easily be done in the clinical or epidemiologic setting, adding an important physiologic measure to BMI to help target and personalize weight control strategies and other treatments to prevent muscle mass loss, potentially improving survival. Findings from this study may thus lead to altered clinical practice. Additionally, insights regarding the role of fat/muscle mass in CRC prognosis may provide new avenues for future research about the role of energy balance in cancer survival