Genetic evidence supporting a causal role of Janus kinase 2 in prostate cancer: a Mendelian randomization study

Background Janus kinase-2 (JAK2) inhibitors are now being tried in basic research and clinical practice in prostate cancer (PCa). However, the causal relationship between JAK2 and PCa has not been uniformly described. Here, we examined the cause-effect relation between JAK2 and PCa.Methods Two-sample Mendelian randomization (MR) analysis of genetic variation data of JAK2, PCa from IEU OpenGWAS Project was performed by inverse variance weighted, MR-Egger, and weighted median. Cochran's Q heterogeneity test and MR-Egger multiplicity analysis were performed to normalize the MR analysis results to reduce the effect of bias on the results.Results Five instrumental variables were identified for further MR analysis. Specifically, combining the inverse variance-weighted (OR: 1.0009, 95% CI: 1.0001-1.0015, p = 0.02) and weighted median (OR: 1.0009, 95% CI: 1.0000-1.0017, p = 0.03). Sensitivity analysis showed that there was no heterogeneity (p = 0.448) and horizontal multiplicity (p = 0.770) among the instrumental variables.Conclusions We found JAK2 was associated with the development of PCa and was a risk factor for PCa, which might be instructive for the use of JAK2 inhibitors in PCa patients.