Angiotensin-converting enzyme inhibitors and the risk of cancer

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Abstract
BACKGROUND A recent observational study suggested that the use of angiotensin‐converting enzyme (ACE) inhibitors protects against cancer in general and against breast and female reproductive tract cancers in particular. To explore these hypotheses, the authors examined cancer risk among users of ACE inhibitors in North Jutland County, Denmark. METHODS Using data from the population‐based Prescription Database of North Jutland County and the Danish Cancer Registry, cancer incidence among 17,897 individuals prescribed ACE inhibitors was compared with expected incidence based on county specific cancer rates during an 8‐year study period with a mean follow‐up of 3.7 years. Standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (95% CIs) were calculated for cancers overall and at selected sites. In addition, the authors performed a direct comparison of users of ACE inhibitors with users of β‐blockers or calcium channel blockers (n = 47,579 individuals) by means of a Cox proportional hazards model. RESULTS Overall, 909 cancer cases were observed among users of ACE inhibitors, with 846 expected based on general population rates, yielding an SIR of 1.07 (95% CI, 1.01–1.15). No risk reductions were observed for cancers of the breast and female reproductive tract, whereas nonsignificantly decreased SIRs were observed for cancers of the esophagus, stomach, and liver. Cancer of the kidney was found in significant excess (SIR, 1.6; 95% CI, 1.1–2.2). Stratification by duration of follow‐up or number of prescriptions revealed no apparent trends, except for a tendency toward decreasing risk with increasing length of follow‐up for smoking‐related cancers. The direct comparison of users of ACE inhibitors with users of β‐blockers or calcium channel blockers yielded results comparable to those derived from the comparison with the general population, with a hazard ratio for cancer overall of 1.01 (95% CI, 0.93–1.09). CONCLUSIONS This large, population‐based cohort study did not confirm a protective effect of ACE inhibitors on the development of cancer. The excess of kidney cancer observed likely reflects a correlation between hypertension and kidney cancer. Further investigation is needed to evaluate the long‐term effects of ACE inhibitors beyond the observation period of this and previous studies. Also, the suggestive evidence of decreased risks for upper digestive system cancers and for smoking‐related cancers over time may warrant additional investigation. Cancer 2001;92:2462–70. © 2001 American Cancer Society.