Association between angiotensin-converting enzyme inhibitors and the risk of lung cancer: a systematic review and meta-analysis

Abstract

Background The association between the use of angiotensin-converting enzyme inhibitors (ACEIs) and lung cancer risk remains controversial. This study evaluated the association between the use of ACEIs and lung cancer risk. Methods Records from five databases were searched from inception to 26 January 2022. Clinical studies involving persons aged ≥18 years with at least one year of follow-up and reporting adverse events, including lung cancer, were recorded with separate outcome reports supplied for the ACEIs and control groups. Data were extracted independently by three authors and pooled using a random-effects model. The primary outcome was lung cancer development. Odds ratios (ORs) with 95% confidence intervals (CIs) and lung cancer-related morbidity were calculated. Results Of 2400 records screened, 13,061,226 patients were included from seven cohort studies and four case–control studies. Pooled results showed that ACEIs use was linked to increased lung cancer risk (OR 1.19, 95% CI 1.05–1.36; P = 0.008), with high heterogeneity (I2 = 98%). Conclusions ACEI usage is a greater risk factor for lung carcinogenesis than angiotensin receptor blocker use, especially in Asian patients. Further randomised controlled trials are needed to confirm the causal association between the use of ACEIs and lung cancer risk.

Association between angiotensin-converting enzyme inhibitor-induced cough and the risk of lung cancer: a Mendelian randomization study

“…Recent clinical studies have shown that lung cancer is a notable adverse event attributable to ACEI use ( Hicks et al, 2018 ; Lin et al, 2020 ; Kristensen et al, 2021 ). A recent meta-analysis ( Wu et al, 2023 ) by the authors of the present study (Wu and Yao) demonstrated that ACEI use is a greater risk factor for lung cancer (up to 1.6%) than angiotensin receptor blocker use, especially among Asian patients.…”

Angiotensin-Converting Enzyme and Hypertension: A Systemic Analysis of Various ACE Inhibitors, Their Side Effects, and Bioactive Peptides as a Putative Therapy for Hypertension

“…Somatic ACE arose as an implication of gene duplication and contains two active sites (Terminal N-and C-domains). The polypeptide chain of somatic ACE is 1,277 amino acids, whereas the testicular ACE is smaller with 701 amino acid residues [63].…”

“…Somatic ACE (sACE) has a significant role in the blood pressure regulatory mechanism (renin-angiotensin system). In somatic ACE, the polypeptide chain is 1,277 amino acids in length [63]. It is involved in the Ang II formation which is a potent vasoconstrictor and also degrades the vasodilator bradykinin, thereby resulting in increased blood pressure [64].…”

“…Testicular ACE has an important role in reproduction and is 701 amino acids in length [63]. It has the same gene sequence as somatic ACE but has a tissue-specific promoter located within intron 12 [66].…”

An angiotensin system inhibitor (losartan) potentiates antitumor efficacy of cisplatin in a murine model of non–small cell lung cancer

“…The role of angiotensin system inhibition (ASI) in modifying the risk of developing lung cancer has been an area of intense study, with important implications should this common class of drugs be found to promote lung cancer. 1 , 2 , 3 , 4 Comparatively little study has been done into the influence ASI may have on treatment of an established lung cancer. Several small retrospective studies have demonstrated a 40% increase in survival in patients incidentally receiving ASI versus those not exposed to ASI and a 47% increase in progression-free survival with ASI use, which was most pronounced with angiotensin receptor binders therapy.…”