Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers Might Be Associated with Lung Adenocarcinoma Risk: A Nationwide Population-Based Nested Case–Control Study

Abstract

Objectives: To analyze the association of the use of different doses of angiotensin II receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) independently with lung cancer risk and to evaluate the lung cancer type that may be related to ARB or ACEI use. Patients and Methods: A nationwide population-based nested case–control study was conducted using Taiwan National Health Insurance Research Database linked to the Taiwan Cancer Registry database between January 1, 2000, and December 31, 2016. The cumulative defined daily dose (DDD) was estimated. We divided all users of ACEI or ARB into three categories based on the DDD of ACEI or ARB: low dose, middle dose, and high dose. Results: We identified 16,091 patients with newly diagnosed lung cancer, and 80,455 controls with hypertension were selected. Univariate and multivariate conditional logistic regressions showed that the independent risk factor for lung cancer was high-dose (≥1095 DDD) ARB use (adjusted odds ratio [OR]: 1.069, 95% confidence interval [CI]: 1.02–1.12, P = 0.003). An increase in lung adenocarcinoma (ADC) risk was associated with middle-dose (adjusted OR: 1.073, 95% CI: 1.01–1.14, P = 0.025) to high-dose (adjusted OR: 1.106, 95% CI: 1.05–1.17, P < 0.001) ARB use and high-dose ACEI use (adjusted OR: 1.095, 95% CI: 1.01–1.19, P = 0.033). No association was observed between different ARB or ACEI dose levels and the risk of lung squamous cell carcinoma and small-cell lung carcinoma. Conclusions: Our results suggest that the use of both ACEI and ARB at a high cumulative dose is associated with the risk of lung ADC. Funding Statement: Taipei Medical University and Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital (Funding Number 10908 & 10909). Declaration of Interests: The authors have no potential conflicts of interest to declare. Ethics Approval Statement: Our protocols were reviewed and approved by the Institutional Review Board of Taipei Medical University (TMU-JIRB No. 201712019).