Resolving the obesity paradox in kidney cancer"

项目总结 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 肥胖患者实际上比体重指数(BMI)较低的人活得更长。这是违反直觉的 这一现象被称为“肥胖悖论”。对肥胖悖论的一种解释是，过度 体重有益于肾癌患者；因此，肥胖的肾癌患者应保持体重增加 生死存亡。然而，这一解释与建议减肥的国家指南直接相反 肥胖的癌症患者。相反，我们认为肥胖悖论可能是研究设计不当造成的。 和分析策略。具体地说，之前的研究比较了肾脏的体重状况和存活率 癌症患者没有考虑(1)确诊前与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 这可能比其他亚型预后更好。如果这些偏见中的任何一个都存在， “关联并不等于因果关系”，先前研究的结果并没有解决体重与体重的关系 干预措施可能会影响肾癌的存活率。在研究这些偏差时，没有任何先前的研究解释过 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 疾病前的患者和可以解释癌症风险因素的特殊统计技术 这增加了死亡率，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)在流行的肾癌病例中，进行敏感性 分析以量化诊断前的重量损失和对撞机偏差对原油的影响程度 体重指数与5年存活率之间的关联，以及2)在发生肾癌的病例中，使用逆概率 加权(IPW)以估计诊断前BMI与调整对撞机死亡率之间的关联 分层偏见。解决围绕RCC“肥胖悖论”的争议需要一个明确的因果关系 框架、适当的分析方法和丰富的纵向数据集，如NIH-AARP饮食和健康 学习。通过结合所有这些元素，我们将产生切中RCC悖论核心的结果 并为今后采取肥胖相关干预措施提高肾癌患者的存活率提供依据。此外，如果 我们的分析证明并消除了RCC生存研究中的偏差，然后本项目将介绍一种 改变癌症存活率观察性研究方法范式的新方法。

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.