The geographically variable mutational signatures observed in this study can be attributed to specific environmental or lifestyle factors. For instance, in Romania, Serbia, and Thailand, the presence of mutational signatures characteristic of aristolochic acid compounds in clear cell renal cell carcinomas suggests exposure to this carcinogen in these regions. On the other hand, in Japan, the high prevalence of a mutational signature of unknown cause in kidney cancer cases indicates a unique environmental or lifestyle factor influencing mutagenesis. Additionally, the higher mutation loads of a ubiquitous mutational signature in countries with higher kidney cancer incidence rates point towards a common environmental exposure contributing to mutagenesis in these regions.