The random-effects inverse variance weighted (IVW) model-based primary MR analysis (OR = 0.94, 95% CI = 0.91–0.97, P = 0.0007) and replication MR analysis (OR = 0.90, 95% CI = 0.85–0.96, P = 0.0006) both provided robust evidence of the causality of genetic liability for the use of agents acting on the renin-angiotensin system on a decreased risk of prostate cancer. Here, REN is linked to prostate cancer.