Frontiers in Pharmacology (Sep 2023)

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

  • Taikang Yao,
  • Taikang Yao,
  • Zhenchao Wu,
  • Zilu Wang,
  • Zilu Wang,
  • Liting Chen,
  • Liting Chen,
  • Beibei Liu,
  • Ming Lu,
  • Ning Shen

DOI
https://doi.org/10.3389/fphar.2023.1267924
Journal volume & issue
Vol. 14

Abstract

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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.

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