Use of Hydrochlorothiazide and Risk of Melanoma and Nonmelanoma Skin Cancer

Julie Rouette, Hui Yin, Anton Pottegård, Krishnarajah Nirantharakumar, Laurent Azoulay*

*Corresponding author for this work

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Introduction: There are concerns that hydrochlorothiazide may increase the risk of incident nonmelanoma (cutaneous squamous cell carcinoma [cSCC], basal cell carcinoma [BCC]) and melanoma skin cancer, with regulatory agencies and societies calling for additional studies. Methods: We conducted a propensity score-matched population-based cohort study using the United Kingdom Clinical Practice Research Datalink. A total of 20,513 new users of hydrochlorothiazide were propensity score matched, in a 1:1 ratio, to new users of other thiazide diuretics between January 1, 1988 and March 31, 2018, with follow-up until March 31, 2019. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for cSCC, BCC, and melanoma, comparing use of hydrochlorothiazide with use of other thiazide diuretics overall, by cumulative duration of use, and cumulative dose. Results: After an 8.6-year median follow-up, hydrochlorothiazide was associated with an increased risk of cSCC (HR 1.50, 95% CI 1.06–2.11). HRs increased with cumulative duration of use, with evidence of an association after 5–10 years (HR 2.10, 95% CI 1.20–3.67) and highest after > 10 years (HR 3.70, 95% CI 1.77–7.73). Similarly, HRs increased with cumulative dose, with higher estimates for ≥ 100,000 mg (HR 4.96, 95% CI 2.51–9.81). In contrast, hydrochlorothiazide was not associated with an increased risk of BCC (HR 1.01, 95% CI 0.91–1.13) or melanoma (HR 0.82, 95% CI 0.63–1.08), with no evidence of duration– or dose–response relationships. Conclusions: Use of hydrochlorothiazide was associated with an increased risk of cSCC and with evidence of a duration– and dose–response relationship. In contrast, no association was observed for BCC or melanoma.

    Original languageEnglish
    JournalDrug Safety
    Volume44
    Issue number1
    Pages (from-to)245-254
    ISSN0114-5916
    DOIs
    Publication statusPublished - Feb 2021

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