Risk of squamous cell carcinoma of the lip and cutaneous melanoma in older Australians using hydrochlorothiazide: A population-based case-control study

Basic Clin Pharmacol Toxicol. 2020 Oct;127(4):320-328. doi: 10.1111/bcpt.13463. Epub 2020 Aug 3.


Recent European and US studies reported increased risks of skin cancers associated with hydrochlorothiazide (HCTZ) treatment. Our study aimed to determine the risk of lip cancer and malignant melanoma among Australians prescribed HCTZ. We conducted a case-control study nested within a population of veterans residing in New South Wales in 2004-2015, using Australian Department of Veterans' Affairs data linked with cancer registrations, hospitalisation and prescription dispensings. Among DVA healthcare card holders 65 years and older, we identified incident cases of squamous cell carcinoma of the lip and of cutaneous melanoma, each matched with up to 20 controls through risk-set sampling. We estimated odds ratios (ORs) associating HCTZ use with each cancer using conditional logistic regression, adjusting for predefined confounders. For lip cancer (45 cases), ever-use of HCTZ yielded an OR of 2.6 (95% CI: 1.4-5.0) and high HCTZ use (≥25 000 mg) an OR of 4.7 (95% CI: 1.6-13.7). For cutaneous melanoma (659 cases), ever-use of HCTZ resulted in an OR of 1.2 (95% CI 1.0-1.5) and high HCTZ use in an OR of 1.2 (95% CI: 0.8-1.8). Our findings align with risk estimates from previous studies and provide further evidence that HCTZ's photosensitising properties may promote carcinogenesis in sun-exposed tissues.

Keywords: Australia; hydrochlorothiazide; lip cancer; malignant melanoma; skin cancer.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Australia / epidemiology
  • Carcinoma, Squamous Cell / etiology*
  • Carcinoma, Squamous Cell / pathology
  • Case-Control Studies
  • Cohort Studies
  • Dermatitis, Phototoxic / complications
  • Female
  • Humans
  • Hydrochlorothiazide / adverse effects*
  • Lip Neoplasms / etiology*
  • Male
  • Melanoma / etiology*
  • Melanoma, Cutaneous Malignant
  • Risk Factors
  • Skin Neoplasms / etiology*


  • Hydrochlorothiazide