Immune-mediated pathways between red blood cell traits and prostate cancer: a causal relationship network based on Mendelian randomization evaluation

Although both the immune and hematopoietic systems play important roles in prostate cancer (PCa), few studies have comprehensively investigated the combined influence of these systems on PCa risk. The datasets used to construct causal networks for evaluation via Mendelian randomization and mediation Mendelian randomization (MMR). Nine analytical approaches were applied to evaluate the causal associations. The findings revealed that red blood cell count (RBC) and red cell distribution width (RDW) were related to a modest increased risk of PCa, while mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were related to a modest reduced risk. Further, MMR analyses identified that HLA-DR on dendritic cells mediated the causal effect of RBC on PCa, with a mediated proportion of 12.09%, and that IgD+ CD38− B cell % B cell mediated the effects of RDW and MCHC on PCa, with mediating proportions of 15.07% and 25.96%, respectively. Moreover, the IgD+ CD38− B cell % lymphocytes mediated the causal effect of MCHC on PCa, with a mediated proportion of 29.03%. RBC, RDW, MCH, and MCHC were related to the risk of PCa. Immune cells act as major mediators in this relationship.