The findings of this study have significant implications for global cancer prevention and public health strategies, especially for kidney cancer and other cancer types with geographic variations in incidence. By identifying multiple geographically variable mutagenic exposures contributing to kidney cancer, there is a need for targeted prevention efforts in regions where specific carcinogens are prevalent. Public health strategies can be tailored to educate populations in high-risk areas about the dangers of these environmental exposures and promote lifestyle modifications to reduce cancer risk. Furthermore, the discovery of unknown mutational signatures highlights the importance of continued research to uncover novel carcinogens and develop preventive measures. Implementing comprehensive cancer screening programs in regions with high incidence rates and integrating genomic data into public health policies can aid in early detection and personalized treatment strategies, ultimately reducing the global burden of kidney cancer and other cancers with geographic disparities in incidence.