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.
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