Hematological parameters as predictors of prostate cancer: A study based on multivariable and bidirectional Mendelian randomization

This study explores the causal relationship between hematologic parameters and prostate cancer (PCa) risk, offering insights into potential biological pathways and clinical implications. We used genome-wide association studies to perform forward and reverse Mendelian randomization (MR) within a 2-sample framework. Additionally, multivariable MR was employed to assess the associations between multiple hematological markers and PCa. Several sensitivity analyses were conducted to ensure the robustness of the findings. Univariable MR analysis showed that genetically predicted mean corpuscular volume (OR: 0.942, 95% CI: 0.891-0.996, P = .035) and mean corpuscular hemoglobin (OR: 0.934, 95% CI: 0.882-0.988, P = .018) were associated with reduced PCa risk. Conversely, increases in eosinophil (OR: 1.081, 95% CI: 1.005-1.163, P = .036) and basophil counts (OR: 1.235, 95% CI: 1.006-1.516, P = .044) were linked to higher PCa risk. Multivariable MR highlighted a stronger association between basophil count and PCa (OR: 1.432, 95% CI: 1.028-1.996, P = .034). Reverse MR indicated that PCa may increase neutrophil (OR: 1.012, 95% CI: 1.001-1.023, P = .031) and red blood cell counts (OR: 1.008, 95% CI: 1.000-1.016, P = .042). Our findings reveal causal associations between hematological parameters and PCa, improving understanding of the genetic links and potential interactions between these markers and PCa risk.