Approved Research

Investigating the causal relationship between chronic kidney disease and renal cell carcinoma, and establishing a polygenic screening model for identifying high-risk renal cell carcinoma patients

Lay summary

Aims: This research project has two primary objectives: 1) to investigate if chronic kidney disease (CKD) causes renal cell carcinoma (RCC), the most common type of kidney cancer, and 2) to develop a polygenic risk score (PRS) to identify people at high risk for RCC so they can get screened and treated early.

Scientific Rationale: CKD affects a lot of people and might raise the risk of getting RCC. But past studies had limitations. We're using a new method (a Mendelian Randomization approach: a scientific method that helps us understand if one thing causes another) to overcome these limitations and to see if CKD really leads to RCC. Additionally, early detection and treatment of RCC are crucial for improving patient outcomes. PRSs, which combine the effect sizes of multiple genetic variants, have shown promise as a tool for risk stratification in various diseases, including cancers. The genetic risk scores we're making can help find high-risk individuals and start treatment sooner. However, it's an area of research that hasn't been explored much.

Project Duration: This research project is expected to be completed within 24 months, including data collection, analysis, PRS development and validation, and preparing a report.

Public Health Impact: By investigating the causal relationship between CKD and RCC and developing a PRS for RCC risk, this study can give us important insights to the field and ultimately improve patient outcomes. Understanding the relationship between CKD and RCC will help inform potential interventions for patients with CKD, potentially reducing their risk of developing RCC. The development of a PRS for RCC will enable targeted screening and early intervention in those at high risk for RCC, leading to improved survival rates and a reduced burden on healthcare systems. Overall, this project holds significant public interest and value by addressing two critical aspects of RCC management, contributing to better RCC prevention, early detection, and personalized care strategies that benefit public health.

Scope extension:

In this study, we aim to address two key objectives. The first is to investigate whether there is a causal relationship between chronic kidney disease (CKD) and renal cell carcinoma (RCC). We will use a Mendelian Randomization approach to examine this relationship, leveraging genetic variants associated with CKD as instrumental variables. By analyzing data from the CKDGen consortium and the UK Biobank, we will be able to draw conclusions about the causality between CKD and RCC, overcoming the limitations of traditional observational studies. The second objective is to develop a polygenic risk score (PRS) for identifying high-risk individuals for RCC. We will use genome-wide association study (GWAS) data from the UK Biobank to identify genetic variants associated with RCC risk. Next, we will create a PRS model by combining the effect sizes of these genetic variants. The PRS will be validated in an independent cohort to assess its accuracy in identifying high-risk individuals. By accomplishing these aims, we hope to improve our understanding of the relationship between CKD and RCC and develop a novel risk prediction tool that can help identify high-risk individuals for targeted screening and early intervention, ultimately reducing the burden of renal cell carcinoma.

Moreover, we intend to expand our focus of renal cell carcinoma to all the urological diseases, including but not limited to malignant of urological cancer, benign prostatic hyperplasia, urolithiasis and so on. Also, we will explore the effect of other potential and possible risk factors (not just chronic kidney disease) on urological diseases. We aim to provide health promotion and medical instructions to the whole urology community.