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

Abstract

Background: Observational studies and meta-analyses have demonstrated a positive correlation between the use of angiotensin-converting enzyme inhibitors (ACEIs) and lung cancer. However, the findings remain controversial; furthermore, the relationship between ACEI-induced cough and lung cancer development remains unknown. We used Mendelian randomization (MR) to verify the association between ACEI use, ACEI-induced cough, and the risk of lung cancer.Methods: We performed a two-sample MR analysis to determine the unconfounded relationships between ACE inhibition, which mimics the effects of ACEIs, and genetic proxies for ACEI-induced cough and lung cancer. Single nucleotide polymorphisms that imitate ACE receptors and ACEI-induced cough were collected and integrated into a meta-analysis of existing genome-wide association studies for various lung cancers. The relationship was quantified using inverse variance weighting, weighted median, and MR-Egger methods.Results: A statistically significant association was observed between ACE inhibition and the risk of small cell lung cancer for Europeans (excluding rs118121655/rs80311894). Associations were identified between ACEI-induced cough and the risk of lung cancer for Europeans, although not for Asians, and between ACEI-induced cough and lung adenocarcinoma (excluding rs360206).Conclusion: Our findings reveal a relationship between ACE inhibition and lung cancer development, as well as a significant association between ACEI-induced cough and a higher risk of lung cancer for Europeans. Patients with hypertension who experience dry cough as a side effect of ACEI use should consider switching to an alternative antihypertensive treatment.

Association Between ACE2 and Lung Diseases

“…63,64 Clinical studies have validated the correlation between elevated ACE2 expression and a more favorable prognosis in non-small cell lung cancer, 65 consistent with the foundational research discussed earlier. A Mendelian randomization study confirmed an increased risk of lung cancer in individuals prescribed formulations of angiotensin-converting enzyme inhibitors, 66 aligning with the conclusions of a meta-analysis that contradicted the protective role of ACE2 against lung cancer. 67…”

Efficacy of traditional Chinese medicine versus angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and their combinations in the treatment of IgA nephropathy: a systematic review and network meta-analysis

“…The efficacy of RAS-blockers is often suboptimal in patients with hyperkalemia and severe renal dysfunction. Moreover, these drugs are often associated with adverse effects including dry cough, edema, and fatigue ( Whitlock et al, 2023 ; Yao et al, 2023 ).…”

An Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC–MS/MS) Method for Qualifying DAPB in Rat Plasma and Application to Pharmacokinetic Studies

“…Angiotensin-converting enzyme inhibitors (ACEIs), suppressing the activity of angiotensin-converting enzyme (ACE) that is responsible for the conversion of angiotensin I to angiotensin II, have been the first-line drugs for improving hypertension [ 4 , 5 ]; however, ACEIs have side effects such as an irritating dry cough, angioedema, and abnormal renal function, which seriously affect the quality of life and health of patients [ 6 , 7 , 8 ]. Therefore, developing a new ACEI drug with fewer side effects is urgent for the treatment of hypertension [ 9 ].…”