Hydrochlorothiazide Use and Risk of Skin Cancer: A Population-Based Retrospective Cohort Study

Pharmacoepidemiol Drug Saf. 2024 Nov;33(11):e70027. doi: 10.1002/pds.70027.

Abstract

Purpose: Hydrochlorothiazide (HCTZ) exposure has been linked to increased skin cancer in Caucasian (white) populations, especially squamous cell carcinoma (SCC), but not basal cell carcinoma (BCC). This study aimed to evaluate and compare skin cancer risks associated with HCTZ- and other antihypertensives use.

Methods: This retrospective cohort study utilized Taiwan's National Health Insurance Research Database. We identified patients aged 20 years and older, newly receiving antihypertensive medications between 2004 and 2015. We calculated the medication possession ratio (MPR) for the first 2 years of treatment to determine patient eligibility and treatment classification, whereby only patients with MPR above 80% were included. These were subsequently categorized by the type of antihypertensives they received, namely HCTZ, other thiazide diuretics, non-thiazide diuretics or non-diuretic antihypertensives. Cox proportional hazards model was used to evaluate skin cancer risks, and these were then classified as SCC or BCC.

Results: Our study included 41 086, 27 402, 19 613, and 856 782 patients receiving HCTZ, other thiazide diuretics, non-thiazide diuretics, and non-diuretic antihypertensives, respectively. We found BCC risks were similar when comparing HCTZ with other thiazides (adjusted hazard ratio: 0.84; 95% CI: 0.54-1.33), non-thiazide diuretics (0.93; 0.51-1.67), and non-diuretic antihypertensives (0.91; 0.66-1.26). We observed a higher SCC risk in the HCTZ group, compared to other thiazides (1.24; 0.74-2.08), non-thiazide diuretics (1.32; 0.70-2.51), and non-diuretic antihypertensives (1.23; 0.87-1.73), although the confidence intervals (CIs) were wide and crossed the null.

Conclusions: We concluded that skin cancer need not be of major concern to physicians when prescribing antihypertensives for an Asian population.

Keywords: antihypertensive agent; basal cell carcinoma and squamous cell carcinoma; hydrochlorothiazide; non‐melanoma skin cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents* / adverse effects
  • Carcinoma, Basal Cell* / chemically induced
  • Carcinoma, Basal Cell* / epidemiology
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / epidemiology
  • Cohort Studies
  • Databases, Factual / statistics & numerical data
  • Female
  • Humans
  • Hydrochlorothiazide* / administration & dosage
  • Hydrochlorothiazide* / adverse effects
  • Hypertension / drug therapy
  • Hypertension / epidemiology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Skin Neoplasms* / chemically induced
  • Skin Neoplasms* / epidemiology
  • Sodium Chloride Symporter Inhibitors / adverse effects
  • Taiwan / epidemiology
  • Young Adult

Substances

  • Hydrochlorothiazide
  • Antihypertensive Agents
  • Sodium Chloride Symporter Inhibitors

Grants and funding