TY - EJOU AU - Zhang, Wei AU - Peng, Xixi TI - Genetic evidence against a causal relationship between myocardial infarction and urological malignancies T2 - Canadian Journal of Urology PY - 2026 VL - 33 IS - 2 SN - 1488-5581 AB - Background: Observational studies have suggested potential associations between myocardial infarction (MI) and cancer risk, but the causal nature of these relationships remains unclear due to confounding factors and reverse causation. We aimed to investigate the bidirectional causal relationships between MI and urinary system cancers using genetic instruments. Methods: We conducted a two-sample Mendelian randomization (MR) analysis using summary statistics from large-scale genome-wide association studies. Genetic variants associated with MI were used as instrumental variables (n = 19 SNPs for prostate cancer [PCa] and malignant neoplasm of kidney [MRN], n = 6 SNPs for bladder cancer, n = 21 SNPs for bladder cancer [BCa] validation). We examined the causal effects of MI on PCa, BCa, and MRN risk, as well as reverse causation. Multiple MR methods were employed, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode approaches. Both discovery and validation datasets were analyzed to ensure robustness. Results: Forward MR analysis revealed no significant causal effect of MI on urinary system cancer risk across all examined malignancies. For PCa, the odds ratios (ORs) ranged from 0.964 to 1.007 across different methods and datasets (all p > 0.05). Similarly, MI showed no causal association with BCa risk (OR = 1.000, 95% CI: 0.999–1.002 in discovery cohort; OR = 1.000, 95% CI: 1.000–1.001 in validation cohort) or MRN risk (OR = 0.989–1.060 across methods in discovery cohort). Reverse MR analysis demonstrated no significant causal effects of PCa or kidney malignancy on MI risk, with ORs ranging from 0.250 to 1.200 (all p > 0.05). Sensitivity analyses confirmed the absence of pleiotropy and heterogeneity. Conclusion: Our genetic evidence does not support causal relationships between MI and urinary system cancers in either direction. The observed associations in epidemiological studies may be attributed to shared risk factors, treatment effects, or residual confounding rather than direct causal mechanisms. These findings have important implications for cancer surveillance strategies in MI patients and understanding cardio-oncology interactions. KW - myocardial infarction; prostate cancer; bladder cancer; malignant neoplasm of kidney; causal inference; genetic epidemiology DO - 10.32604/cju.2026.072565