Causal relationship between immune cells and bladder cancer: a bi-directional Mendelian randomization study

Abstract Background and Objectives: Previous studies have explored the role of immune cells on bladder cancer（BCa）. This bi-directional Mendelian randomization (MR) study further assessed 731 immunocyte phenotypes on whether BCa a causal relationship exists and provides some evidence of causality. Methods: The summary data for immune cell phenotypes was derived from a study cohort, including 3,757 individuals from Sardinia with data on 731 immune cell phenotypes. The summary data for BCa were obtained from their respective genome-wide association studies (GWAS). We used inverse variable weighting (IVW) as the primary analysis method. In addition, we simultaneously employed multiple analytical methods, including MR-Egger, weighted mode, simple mode, and weighted median, to strengthen the final results. Finally, sensitivity analyses were conducted to verify the stability and feasibility of the data. Results: 16 immune cell traits involving the four immunological signal types (MFI, RC, AC, and MP) were shown to be significantly correlated with the risk of BCa in our investigation. BCa was positively correlated with 5 immune cell traits (P < 0.05, OR > 1); However, the remainder BCa incidence decreases by 11 traits (OR<1, P<0.05). Furthermore, none of them revealed reverse causality, heterogeneity, or horizontal pleiotropy (P > 0.05). Conclusions: Through a comprehensive bi-directional MR analysis, we were able to reveal a complicated causal link between several immunological phenotypes and BCa, focusing on the intricate network of interactions between the immune system and BCa. The results of this study provide fresh viewpoints and resources for investigating immunotherapeutic targets and BCa preventive tactics.