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Hydrochlorothiazide and the risk of skin cancer. A scientific statement of the British and Irish Hypertension Society

Journal of Human Hypertension volume 33, pages 257–258 (2019)Cite this article

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Hydrochlorothiazide (HCTZ) is a thiazide diuretic which has been available for clinical use for more than 5 decades and is still amongst the most frequently prescribed antihypertensive drugs in Europe. The effectiveness of thiazides in preventing all types of cardiovascular morbidities and mortality has been confirmed in randomised controlled trials and meta-analyses [1]. In the UK, it is usually employed as a fixed-dose combination with other blood pressure lowering agents (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, calcium channel blockers) for the treatment of hypertension or in combination with other diuretics (such as amiloride and spironolactone) for oedema and congestive heart failure.

A recent series of articles from various Danish nationwide demographic and health registries have associated HCTZ use with increased risk of lip and skin cancer [2,3,4,5]. This finding has received much publicity and has caused concerns amongst physicians, and their patients. Regarding melanoma [4], 413 cases were identified among “high-users” of HCTZ yielding an adjusted odd ratio (OR) of 1.22 (95% confidence interval (CI): 1.09–1.36) compared to controls, with no cumulative dose–response pattern. For non-melanoma skin cancers [3], high use of HCTZ was associated with ORs of 1.29 (95% CI: 1.23–1.35) for basal skin cancer and 3.98 (95% CI: 3.68–4.31) for squamous cell carcinoma. Use of other diuretics, including thiazides (bendroflumethiazide) and thiazide-like (indapamide), was not associated with increased risk. For lip cancer [2], ever-use of HCTZ was associated with an adjusted OR for squamous cell carcinoma of 2.1 (95% CI: 1.7–2.6), increasing to 3.9 (95% CI: 3.0–4.9) for use ≥25,000 mg. Risk increased with increasing cumulative amount, duration (over 22 years for high dose and 44 years for low dose) and intensity of HCTZ use. At face value, these numbers appear alarming but represent only a relative rather than an absolute risk. In the UK, melanoma accounts for 4% of all new cancer cases and 1% of all cancer deaths [6], while non-melanoma accounts for less than 1% of all cancer deaths [7]. Therefore, these high-relative increases will account for a very small number of cases over the long period. More importantly, conclusions regarding causality cannot be derived from observational data which are not fully adjusted for confounders, as occurs in adequately sized randomised trials. None of the studies took into account ultraviolet (UV) radiation exposure, skin phenotype and tobacco smoking, which are major risk factors for these cancers. These conclusions cannot be easily generalised for ethnic minorities as no data regarding non-white ethnic subjects were provided in the studies.

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References

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  1. Department of Clinical Pharmacology, King’s College London, London, UK

    Luca Faconti, Albert Ferro, Andrew J. Webb & Phil J. Chowienczyk

  2. School of Life-course Sciences, King’s College London, London, UK

    J. Kennedy Cruickshank

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  1. Luca Faconti
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Faconti, L., Ferro, A., Webb, A.J. et al. Hydrochlorothiazide and the risk of skin cancer. A scientific statement of the British and Irish Hypertension Society. J Hum Hypertens 33, 257–258 (2019). https://doi.org/10.1038/s41371-019-0190-2

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