Background:

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.

Method:

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.

Result:

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%.

Conclusion:

RBC, RDW, MCH, and MCHC were related to the risk of PCa. Immune cells act as major mediators in this relationship.