Renin–Angiotensin System Inhibitor Use and Cancer Incidence Among UK Biobank Participants: A Prospective Cohort Study

BACKGROUND: Renin-angiotensin system (RAS) inhibitors may influence cancer incidence, but previous findings have been inconsistent. We aimed to evaluate the associations of RAS inhibitor use with overall and site-specific cancer incidence. MATERIALS AND METHODS: Participants receiving antihypertensive treatment without prior invasive cancer (except non-melanoma skin cancer) were identified from the UK Biobank. Individuals with missing covariate data were excluded. Participants were classified as ACEI users, ARB users, or RAS inhibitor non-users, defined as participants receiving antihypertensive medications other than ACEIs or ARBs. Outcomes included overall cancer incidence and site-specific cancers. Inverse probability of treatment-weighted Cox proportional hazards models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among 94,696 participants followed for a mean of 11.5 years, 42,930 were ACEI users, 17,681 were ARB users, and 34,085 were RAS inhibitor non-users. No significant associations were observed between ACEI or ARB use and overall cancer incidence. In site-specific analyses, ARB use showed a modest association with higher prostate cancer incidence compared with ACEI use (HR = 0.90; 95% CI, 0.82-0.99) and RAS inhibitor non-use (HR = 1.14; 95% CI, 1.02-1.27). ACEI use was associated with lower bladder cancer incidence compared with RAS inhibitor non-use (HR = 0.71; 95% CI, 0.54-0.93). CONCLUSION: RAS inhibitor use was not associated with overall cancer incidence in this large cohort of antihypertensive medication users. Although modest associations were observed between ARB use and prostate cancer incidence and between ACEI use and bladder cancer incidence, these findings should be interpreted cautiously and require confirmation in future studies.