Background
To investigate the causal relationship between liver function biomarkers and prostate cancer (PCa) in European and East Asian populations using various forms of Mendelian Randomization (MR) and statistical analyses.
Methods
Single nucleotide polymorphism (SNP), which is strongly associated with exposure factors, was selected as an instrumental variable from genome-wide association studies (GWAS). Inverse variance weighting (IVW), weighted median (WM), MR-Egger, weighted mode, and simple mode were used to investigate the causal relationship between exposure and outcome, and sensitivity analyses were performed to verify the robustness of the results.
Results
Univariate MR analysis suggested a causal relationship between ALT (OR:0.85, 95% CI(0.75,0.95), P:0.005) and AST (OR:0.90, 95% CI(0.81,1.00), P:0.045) and a reduced risk of PCa in European populations, and a causal relationship between total bilirubin (OR:0.94, 95% CI(0.88,1.00), P:0.049) and direct bilirubin (OR:0.91, 95% CI(0.84,0.99), P:0.022) were causally associated with reduced PCa risk in the East Asian population. The association between total bilirubin (OR:0.74, 95% CI(0.55,0.99), P:0.044) and PCa remained significant after multivariate MR analysis adjusting for confounders. In the reverse MR analysis, a causal relationship between PCa and reduced ALT (OR:0.93, 95% CI(0.88,0.98), P:0.007) was found only in the East Asian population. Sensitivity analyses did not reveal heterogeneity or horizontal pleiotropy.
Conclusion
There are differences in the causal relationship between liver function biomarkers and PCa in European and East Asian populations. ALT and AST are protective factors for PCa in European populations, and total bilirubin and direct bilirubin in East Asian populations. PCa decreases ALT levels in East Asian populations, which may be one of the characteristic manifestations of PCa paraneoplastic syndrome. Overall, these findings provide ideas for clinical prevention, monitoring and treatment of PCa.