Causal Associations between Prostate Cancer and Various Hematological Parameters: Insights from Multivariable and Bidirectional Mendelian Randomization Analyses

Purpose This study aims to investigate the causal relationship between hematologic parameters and the risk of developing PCa, employing a rigorous and methodical scientific approach. Methods We applied genome-wide association studies (GWAS) to conduct both forward and reverse Mendelian randomization (MR) analyses within a two-sample framework. We further undertook multivariable MR analyses to investigate the associations between diverse hematological parameters and PCa. To validate the robustness of our results, we implemented several sensitivity analysis techniques. Results In our univariable MR analysis, genetically predicted mean corpuscular volume (Odds Ratio [OR]: 0.942, 95% Confidence Interval [CI]: 0.891–0.996, P=0.035) and mean corpuscular hemoglobin (OR: 0.934, 95% CI 0.882–0.988, P=0.018) in red blood cells were associated with a decreased risk of PCa. Moreover, MR analysis revealed that genetically predicted increases in eosinophil count (OR: 1.081, 95% CI 1.005–1.163, P=0.036) and basophil count (OR: 1.235, 95% CI 1.006–1.516, P=0.044) were linked to an elevated risk of PCa (all P<0.05). In the multivariable analysis, we found that basophil count was associated with an increased incidence of PCa (OR:1.432, 95% CI 1.028–1.996, P=0.034). In the reverse MR analysis, we observed that genetically predicted PCa was associated with an increase in neutrophil count (OR: 1.012, 95% CI: 1.001–1.023, P=0.031) and red blood cell count (OR: 1.008, 95% CI: 1.000–1.016, P=0.042). Conclusion In conclusion, our investigation elucidates the causal associations between specific hematological parameters and PCa. These insights contribute significantly to our understanding of the genetic determinants of PCa and their potential interactions with various hematological parameters.