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Use of Hydrochlorothiazide and Risk of Melanoma and Nonmelanoma Skin Cancer

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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.

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Authors and Affiliations

Authors

Corresponding author

Correspondence to Laurent Azoulay.

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Funding

This work was supported by a Foundation Scheme grant from the Canadian Institutes of Health Research (FDN-143328). JR is the recipient of a Doctoral Award from the Canadian Institutes of Health Research (FRN-152254). LA holds a Chercheur-Boursier Senior Award from the Fonds de Recherche du Québec—Santé and is the recipient of a William Dawson Scholar award from McGill University. Researchers were independent from the funding sources. The funding sources had no influence on the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Conflicts of interest

JR received consulting fees for work unrelated to this project from Biogen. LA received consulting fees from Janssen and Pfizer for work unrelated to this paper. AP reports participation in research projects funded by Alcon, Almirall Astellas, AstraZeneca, Boehringer-Ingelheim, Novo Nordisk, Servier and LEO Pharma, all with funds paid to the institution where he was employed (no personal fees) and with no relation to the work reported in this paper. KN received research funding from AstraZeneca, Vifor and CSL Behring and personal fees from MSD, Sanofi and Boehringer Ingelheim, all unrelated to this study. HY has no conflicts of interest to disclose.

Ethical approval

The study protocol was approved by the Independent Scientific Advisory Committee of the CPRD (protocol number 19_279A) and the Research Ethics Board of the Jewish General Hospital, Montreal, Canada (number 2020-2207).

Consent to participate

Not applicable.

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Not applicable.

Availability of data and materials

The data cannot be shared publicly due to patients’ privacy, as per the Clinical Practice Research Datalink policy.

Code availability

The codes cannot be shared publicly, as per the Lady Davis Institute—Centre for Clinical Epidemiology policy.

Author contributions

Conception and planning of the work that led to the manuscript (JR, HY, LA). Acquisition, analysis and interpretation of the data (JR, HY, AP, KN, LA). Drafting and/or critical revision of the manuscript for important intellectual content (JR, HY, AP, KN, LA). Approval of the final submitted version of the manuscript (JR, HY, AP, KN, LA).

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Rouette, J., Yin, H., Pottegård, A. et al. Use of Hydrochlorothiazide and Risk of Melanoma and Nonmelanoma Skin Cancer. Drug Saf 44, 245–254 (2021). https://doi.org/10.1007/s40264-020-01015-1

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  • DOI: https://doi.org/10.1007/s40264-020-01015-1

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