Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

ACE inhibitors and the risk of lung cancer—is there causality?

British Journal of Cancer volume 129, pages 570–571 (2023)Cite this article

Subjects

A current debate relates to the risk of cancer associated with some antihypertensive drugs [1]. This includes both angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB). A number of ARB have been withdrawn as there are concerns about an increased risk of cancer secondary to carcinogenic contaminants [2]. Wu’s [3] meta-analysis of ACEI observational studies reported an increased incidence of lung cancer vs. control (OR 1.19, CI 1.05–1.36). Their assertion “ACE inhibitors is a relevant factor for lung carcinogenesis and…carries greater risk than use of ARB’s…and the findings provide medication guidance” is however incorrect.

The renin-angiotensin aldosterone system (RAAS) is expressed locally in most body tissues [4]. Although both ACEI and ARB are RAAS inhibitors, each class has unique modes of action. ACEI suppress angiotensin II (AngII) and upregulate bradykinin levels; ARB block the AT1 receptor, upregulate AngII but have no impact on bradykinin [5]. Therefore, there is biological plausibility that ACEI and ARB may differ as it relates to carcinogenesis [4].

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Meta-regression analysis of cumulative exposure to ARB and risk of lung cancer [10].

Data availability

None.

References

  1. Copland E, Canoy D, Nazarzadeh M, Bidel Z, Ramakrishnan R, Woodward M, et al. Antihypertensive treatment and risk of cancer: an individual participant data meta-analysis. Lancet Oncol. 2021;22:558–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Berrido AM, Byrd JB. Angiotensin receptor blockers and the risk of cancer: insights from clinical trials and recent drug recalls. Curr Hypertens Rep. 2020;22:20.

    Article  PubMed  Google Scholar 

  3. Wu Z, Yao T, Wang Z, Liu B, Wu N, Lu M, et al. Association between angiotensin-converting enzyme inhibitors and the risk of lung cancer: a systematic review and meta-analysis. Br J Cancer. 2023;128:168–176.

    Article  CAS  PubMed  Google Scholar 

  4. Almutlaq M, Alamro AA, Alamri HS, Alghamdi AA, Barhoumi T. The effect of local renin angiotensin system in the common types of cancer. Front Endocrinol. 2021;12:736361.

    Article  Google Scholar 

  5. Strauss MH, Hall AS. Angiotensin receptor blockers do not reduce risk of myocardial infarction, cardiovascular death, or total mortality: further evidence for the ARB-MI Paradox. Circulation. 2017;135:2088–90.

    Article  CAS  PubMed  Google Scholar 

  6. Franklin JM, Patorno E, Desai RJ, Glynn RJ, Martin D, Quinto K, et al. Emulating randomized clinical trials with nonrandomized real-world evidence studies: first results from the RCT DUPLICATE Initiative. Circulation. 2021;143:1002–13.

    Article  PubMed  Google Scholar 

  7. Helgeson SA, Waddle MR, Burnside RC, Debella YT, Lee AS, Burger CD, et al. Association between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and lung cancer. South Med J. 2021;114:607–13.

    Article  CAS  PubMed  Google Scholar 

  8. Sipahi I, Chou J, Mishra P, Debanne SM, Simon DI, Fang JC. Meta-analysis of randomized controlled trials on effect of angiotensin-converting enzyme inhibitors on cancer risk. Am J Cardiol. 2011;108:294–301.

    Article  CAS  PubMed  Google Scholar 

  9. Collaboration ARBT. Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138,769 individuals. J Hypertens. 2011;29:623–35.

    Article  Google Scholar 

  10. Sipahi I. Risk of cancer with angiotensin-receptor blockers increases with increasing cumulative exposure: meta-regression analysis of randomized trials. PLoS ONE. 2022;17:e0263461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Levy BI, Mourad JJ. Renin Angiotensin blockers and cardiac protection: from basis to clinical trials. Am J Hypertens. 2022;35:293–302.

Download references

Funding

None.

Author information

Authors and Affiliations

  1. University of Toronto, North York General Hospital, Toronto, ON, Canada

    Martin H. Strauss

  2. Leeds School of Medicine, University of Leeds, Leeds, UK

    Alistair S. Hall

Author notes

  1. Unaffiliated.

    • Ilke Sipahi
Authors
  1. Martin H. Strauss
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ilke Sipahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alistair S. Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors equally contributed.

Corresponding author

Correspondence to Martin H. Strauss.

Ethics declarations

Competing interests

Dr. ASH has received lecture honoraria from Servier a manufacturer of an ACE inhibitor. Dr. MHS has received honoraria for lecture honoraria and advisory boards from Servier a manufacturer of an ACE inhibitor. Dr. IS has received lecture honoraria from Novartis, Boehringer-Ingelheim, Sanofi, Sandoz, Bristol-Myers Squibb, Bayer, Pfizer, Ranbaxy, Servier and ARIS and served on advisory board for Novartis, Sanofi, Servier, Bristol-Myers Squibb, Pfizer, Bayer and I.E. Ulagay some of which manufacture ACE inhibitors or ARB.

Ethics approval and consent to participate

Not applicable.

Consent for publication

All authors consent, the figure included is copyrighted by Dr. IS and was previously published.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Strauss, M.H., Sipahi, I. & Hall, A.S. ACE inhibitors and the risk of lung cancer—is there causality?. Br J Cancer 129, 570–571 (2023). https://doi.org/10.1038/s41416-023-02346-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41416-023-02346-3

Search

Advanced search

Quick links