Use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers and cancer risk: a meta-analysis of observational studies

Background: Epidemiologic studies have reported inconsistent findings regarding the association between the use of angiotensin-converting-enzyme (ACE) inhibitors or angio tensin-receptor blockers and the risk of cancer. We performed a meta-analysis of observational studies to assess the association. Methods: We searched MEDLINE, EMBASE and the Cochrane Library to identify studies through January 2011. Two evaluators independently reviewed and selected articles of cohort and case-control studies on the basis of predetermined selection criteria. Results: Of 3970 screened articles, 12 cohort studies and 16 case-control studies were selected for analysis. We found no significant association between the use of ACE inhibitors or angiotensin-receptor blockers and the overall risk of cancer (relative risk [RR] 0.96, 95% confidence interval [CI] 0.90-1.03). We found a decreased risk of cancer associated with use of either medication when we restricted the analyses to cohort and nested case-control studies (RR 0.90, 95% CI 0.83-0.97) or to studies with long-term follow-up of more than five years (RR 0.89, 95% CI 0.83-0.96). In the subgroup meta-analyses by cancer site, a decreased risk was identified for esophageal cancer, whereas an increased risk was found for melanoma and kidney cancer. Interpretation: No significant association was found between the use of ACE inhibitors or angiotensin-receptor blockers and overall risk of cancer. A possible beneficial effect associated with use of either medication was suggested in sensitivity analyses, including those of studies with long-term follow-up. Large randomized controlled trials with long-term follow-up are needed to specifically test the effect of each of these medications on the risk of cancer.