Causal relationship between the plasma lipidome and urological cancers: A two-sample Mendelian randomization study

The plasma lipidome has been found to be closely related to inflammation, obesity, aging, and other diseases, including various cancers. However, the causal relationship between specific plasma lipid species and the risk of urological cancers remains unclear. This study aimed to investigate the causal relationship between 179 lipid species and 3 common types of urological cancers using a two-sample Mendelian randomization (MR) approach. Large-scale genome-wide association study datasets of 179 lipid species were analyzed to evaluate the association between the plasma lipidome and urological cancers, including bladder cancer, kidney cancer, and prostate cancer. The inverse variance weighted method was employed as the primary analysis approach, supplemented by MR-Egger regression, weighted median, weighted mode, and simple mode methods to ensure the reliability of the findings. Sensitivity analyses, including Cochran Q test, MR-Egger intercept test, MR Pleiotropy Residual Sum And Outlier, and leave-one-out analysis, were performed to assess the stability and robustness of the causal relationship. The inverse variance weighted analysis showed that higher levels of sterol ester (SE) (27:1/16:0) and other plasma lipidome were causally associated with increased bladder cancer risk. Similarly, elevated levels of phosphatidylcholine (16:0_22:6) and others were linked to increased kidney cancer risk. For prostate cancer, higher levels of SE (27:1/17:0) and others were associated with increased risk, while higher levels of SE (27:1/18:2) and others were associated with decreased risk. The study provides strong evidence for the causal relationships between plasma lipidome and bladder, kidney, and prostate cancers. These findings illuminate complex lipid metabolism pathways in urinary system cancer etiology and highlight specific lipid structures' differential impact on cancer risk. This research lays a foundation for further exploring biological mechanisms and developing early screening tools and targeted therapies for urological cancers.