Clear cell renal cell carcinoma (ccRCC) is the most common and deadly subtype type of cancer affecting the kidney. People with obesity have a much higher risk of developing ccRCC than people without obesity, for reasons that are incompletely understood. We and others have shown that people with obesity accumulate excess fat in the kidney. Excess fat in other organs such as the liver and pancreas has been shown to contribute to cancer in those organs. However, whether excess fat in the kidney may contribute to kidney cancer has not been studied. One characteristic of ccRCC is accumulation of excess fat in cancer cells. This fat accumulation has traditionally been thought to occur after cancer...

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Clear cell renal cell carcinoma (ccRCC) is the most common and deadly subtype type of cancer affecting the kidney. People with obesity have a much higher risk of developing ccRCC than people without obesity, for reasons that are incompletely understood. We and others have shown that people with obesity accumulate excess fat in the kidney. Excess fat in other organs such as the liver and pancreas has been shown to contribute to cancer in those organs. However, whether excess fat in the kidney may contribute to kidney cancer has not been studied. One characteristic of ccRCC is accumulation of excess fat in cancer cells. This fat accumulation has traditionally been thought to occur after cancer develops. This project will test the novel, paradigm-shifting hypothesis that fat accumulation in the kidney occurring before cancer develops may cause damage in the kidney that leads to ccRCC. This paradigm-shifting hypothesis is this project's principal innovation. By testing this innovative hypothesis, this project aims to better understand how kidney cancer develops, and why people with obesity are more at risk. In the short term, this project has the potential to open new avenues for research on kidney cancer biology and prevention. The ultimate applicability of this research is that it will lay the foundation for future development and implementation of new, logical strategies for the prevention of kidney cancer in people at risk, potentially resulting in many lives saved. This project addresses the FY21 KCRP Focus Area "Conduct basic biology research to better understand etiology and cancer progression, metastatic disease, refractory disease and therapeutic resistance, genetic and environmental risk factors and the prevention of kidney cancer."

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