Abstract:Objective To explore the potential causal associations between 731 immune-cell phenotypes and urological malignancies (prostate cancer, bladder cancer, and kidney cancer) using Mendelian randomization (MR) and reverse MR. Methods Summary statistics for immune cells, prostate cancer, bladder cancer, and kidney cancer were collected from the Genome-Wide Association Study database. A two-sample MR analysis was performed to assess the causal relationships between 731 immune-cell phenotypes and prostate cancer, bladder cancer, and kidney cancer. The inverse variance weighted (IVW) method was used for the primary analysis, and the corresponding P values were subjected to multiple-testing corrections using the false discovery rate (FDR). Sensitivity analyses were conducted to evaluate the robustness of the main findings. Finally, reverse MR analysis was performed to explore potential reverse causality. Results The IVW method identified 46 immune-cell phenotypes associated with prostate cancer (23 protective and 23 risk), 34 with kidney cancer (17 protective and 17 risk), and 38 with bladder cancer (18 protective and 20 risk). After multiple-testing correction using the FDR, 4 immune-cell phenotypes (immunoglobulin [Ig]D+CD24+ B cell level, CD24+CD27+ lymphocyte level, human leukocyte antigen [HLA] DR+ T cell absolute count level, and CD16-CD56+ natural killer cell level) showed significant associations with prostate cancer risk, and 4 immune-cell phenotypes (IgD+CD38- lymphocyte level, CD127- CD8bright T cell absolute count level, CD11c+ myeloid dendritic cell level, and HLA DR+ B cell level) showed significant associations with kidney cancer risk (all FDR < 0.3). The reverse MR analysis found no positive results between prostate cancer or renal cell carcinoma and the aforementioned immune cells. Conclusion There are potential causal relationships between immune cells and both prostate cancer and kidney cancer, which may provide new directions for exploring early screening strategies and biological mechanisms for urological malignancies, and is also crucial for developing more effective immunotherapies.