Hydrochlorothiazide use ups risk of in situ, invasive SCC, BCC

High cumulative exposure to hydrochlorothiazide (HCTZ) may result in the development of keratinocyte carcinoma and invasive squamous cell carcinoma (SCC), a study has shown, noting that sun protective behaviours alone may not be enough to eliminate the carcinogenic potential of HCTZ.

The authors characterized the association between use of HCTZ and invasive SCC, SCC in situ (SCCis), and basal cell carcinoma (BCC) in this population-based case-control study. A total of 6,880 patients diagnosed with first-time BCC, SCCis, and invasive SCC between 2003 and 2017 in Iceland, as well as 69,620 population controls, were included.

Multivariate odds ratios (ORs) for keratinocyte carcinoma associated with HCTZ use were calculated using conditional logistic regression analyses.

A cumulative dose of HCTZ above 37,500 mg correlated with a heightened risk of invasive SCC (OR, 1.69, 95 percent confidence interval [CI], 1.04–2.74). In addition, users of HCTZ were found to have an elevated risk of SCCis (OR, 1.24, 95 percent CI, 1.01–1.52) and BCC (OR, 1.14, 95 percent CI, 1.02–1.29).

The study was limited by its retrospective nature, with the resulting inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities, the authors said.

These findings support those of a recent study in Australia, which found further evidence that the photosensitizing properties of HCTZ could promote carcinogenesis in sun-exposed tissues.

For instance, ever-use of HCTZ (OR, 2.6, 95 percent CI, 1.4–5.0) and high HCTZ use (OR, 4.7, 95 percent CI, 1.6–13.7) were associated with a high risk of lip cancer. Ever-use (OR, 1.2, 95 percent CI, 1.0–1.5) and high use of HCTZ (OR, 1.2, 95 percent CI, 0.8–1.8) also correlated with an increased risk of cutaneous melanoma. [Basic Clin Pharmacol Toxicol 2020;127:320-328]