Resolving the obesity paradox in kidney cancer"

解决肾癌的肥胖悖论”

• 批准号: 9231802
• 负责人: Whitney Ragan Robinson
• 金额: $ 9.93万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-12 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9231802
• 关键词: Address; Affect; Behavioral; Biological; Body Weight decreased; Body mass index; Cancer Patient; Cancer Survivor; Cancer Survivorship; Clinical Data; Clinical Research; Conflict (Psychology); Data; Diabetes Mellitus; Diagnosis; Diet; Disease; Elements; Epidemiologic Methods; Epidemiology; Etiology; Failure; Future; Goals; Guidelines; Health; Heart; Heart failure; Incidence; Intervention; Intuition; Knowledge; Malignant Neoplasms; Methods; Obesity; Observation in research; Overweight; Patients; Probability; Recommendation; Renal Cell Carcinoma; Renal carcinoma; Research; Research Design; Risk; Risk Factors; Role; Stratification; Techniques; United States National Institutes of Health; Weight; Weight Gain; analytical method; base; cancer risk; cancer subtypes; cancer survival; disorder control; disorder risk; hemodynamics; improved; innovation; longitudinal dataset; mortality; novel strategies; outcome forecast; population based; prospective; survivorship; urologic; wasting

PROJECT SUMMARY Obesity increases the risk of kidney cancer. But, paradoxically, clinical studies of kidney cancer patients find that obese patients actually live longer than those with lower body mass index (BMI). This counter-intuitive phenomenon is known as the “obesity paradox.” One interpretation of the obesity paradox is that excess weight benefits kidney cancer patients; therefore, obese kidney cancer patients should stay heavy to increase survival. However, this interpretation is in direct opposition to national guidelines that advise weight loss for obese cancer patients. Instead, we believe that the obesity paradox could result from inadequate study design and analytic strategies. Specifically, previous studies that compared weight status and survival among kidney cancer patients did not account for (1) disease-related weight loss before diagnosis, (2) kidney cancer risk factors that are stronger predictors of mortality than obesity is, and (3) obesity-related kidney cancer subtypes that may have more favorable prognosis than other subtypes. If any of these biases are present then, “Association does not equal causation,” and the results from prior research do not address how weight-related interventions could affect RCC survival. No prior study has accounted for these biases when studying the obesity paradox in kidney cancer patients. Fortunately, by using longitudinal data to study kidney cancer patients before they get the disease and special statistical techniques that can account for cancer risk factors that increase mortality, we can estimate how excess weight actually affects kidney cancer survival. Using the NIH-AARP Diet and Health Study, the Specific Aims are: 1) Among prevalent RCC cases, perform a sensitivity analysis to quantify the degree to which pre-diagnosis weight loss and collider bias could affect the crude association between BMI and 5-year survival, and 2) Among incident RCC cases, use inverse-probability weighting (IPW) to estimate the association between pre-diagnosis BMI and mortality adjusted for collider stratification bias. Resolving the controversy around the RCC “obesity paradox” requires an explicitly causal framework, appropriate analytic methods, and a rich, longitudinal data set like the NIH-AARP Diet and Health Study. By combining all of these elements, we will produce results that get to the heart of the RCC paradox and provide the basis for future obesity-related interventions to improve survival for RCC patients. Further, if our analyses demonstrate and eliminate biases in RCC survivorship research, then this project will introduce a new approach that shifts the paradigm of methods used in observational research on cancer survival.

项目摘要 肥胖会增加患肾癌的风险。但是，矛盾的是，对肾癌患者的临床研究发现， 肥胖患者实际上比那些身体质量指数（BMI）较低的人活得更长。这种反直觉 这一现象被称为“肥胖悖论”。对肥胖悖论的一种解释是， 体重对肾癌患者有益;因此，肥胖肾癌患者应保持体重，以增加 生存然而，这种解释与建议减肥的国家指导方针直接相反。 肥胖的癌症患者。相反，我们认为肥胖悖论可能是由于研究设计不当造成的。 分析战略。具体来说，以前的研究比较了肾脏疾病患者的体重状况和生存率， 癌症患者没有考虑（1）诊断前疾病相关的体重减轻，（2）肾癌风险 比肥胖更能预测死亡率的因素，以及（3）肥胖相关的肾癌亚型 可能比其他亚型有更好的预后。如果这些偏见中的任何一个存在， “关联不等于因果关系”，先前的研究结果并没有解决体重相关的问题。 干预可能会影响RCC的生存。没有先前的研究已经考虑到这些偏见时，研究 肾癌患者的肥胖悖论幸运的是，通过使用纵向数据来研究肾癌， 在他们患病之前，以及特殊的统计技术，可以解释癌症风险因素， 增加死亡率，我们可以估计超重实际上是如何影响肾癌存活率的。使用 NIH-AARP饮食与健康研究，具体目的是：1）在肾癌流行病例中， 分析，以量化诊断前体重减轻和碰撞机偏差可能影响原油的程度 BMI与5年生存率之间的关系，以及2）在偶发RCC病例中，使用逆概率 加权（IPW），以估计诊断前BMI与经碰撞校正的死亡率之间的相关性 分层偏差解决围绕RCC“肥胖悖论”的争议需要明确的因果关系 框架，适当的分析方法，以及丰富的纵向数据集，如NIH-AARP饮食和健康 Study.通过结合所有这些因素，我们将产生的结果，得到的核心RCC悖论 并为未来肥胖相关的干预措施提供基础，以提高RCC患者的生存率。进而如果 我们的分析证明并消除了RCC生存率研究中的偏见，然后本项目将介绍一个 这是一种新的方法，改变了癌症生存观察研究中使用的方法的范式。