Use of hydrochlorothiazide and risk of skin cancer: a nationwide Taiwanese case–control study

Abstract

Background The antihypertensive agent hydrochlorothiazide has been associated with increased risks of non-melanoma skin cancer (NMSC) and possibly some melanoma subtypes. Previous studies were, however, conducted in predominantly Caucasian populations. We therefore examined the association between hydrochlorothiazide and skin cancer risk in an Asian population. Methods By using Taiwan’s National Health Insurance Research Database (NHIRD), we conducted three separate case–control studies of lip cancer, non-lip non-melanoma skin cancer and melanoma. Cases (n = 29,082) with a first-ever skin cancer diagnoses (2008–2015) were matched 1:10 to population controls. We estimated odds ratios (ORs) associating hydrochlorothiazide use with skin cancer risk by using conditional logistic regression. Results Hydrochlorothiazide use showed no overall association with any of the three outcomes: ORs for high cumulative use of HCTZ (≥50,000 mg) were 0.86 (95% CI 0.09–7.81) for lip cancer, 1.16 (95% CI 0.98–1.37) for non-lip NMSC and 1.07 (95% CI 0.65–1.76) for melanoma. There was some evidence of a dose–response pattern for non-lip NMSC, with an OR of 1.66 (95% CI 0.82–3.33) for 100,000–149,999 mg of HCTZ. The null findings were robust across subgroup and sensitivity analyses. Conclusion Use of HCTZ appears safe in terms of skin cancer risk in an Asian population.

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

“…Likewise, our measures of cumulative use may be lower than the true values. A recent study from Taiwan found no associations between either lip cancer or melanoma and HCTZ use in the Taiwanese population, suggesting that HCTZ users with Caucasian skin type may be most at risk of developing these skin cancers 35 . We did not have data for skin type (or skin colour or ethnic background), but the majority of the Australian population is of European descent 36 .…”

Association between Use of Hydrochlorothiazide and Nonmelanoma Skin Cancer: Common Data Model Cohort Study in Asian Population

“…These inconsistent and uncertain observations between studies emphasize the challenges we face when interpreting the findings in real-world observational studies. In fact, despite the increased risk of skin cancer associated with the use of HCTZ in white Westerners, there is no evidence that the carcinogenic effect of HCTZ is substantial in the Asian population [ 19 ], whose incidence of skin cancer is much lower [ 20 ]. Therefore, to elucidate the association between the use of HCTZ and skin cancer clearly, a nationwide observational study with qualified assessment and fewer biases should be conducted through a distributed data system with standardized protocol.…”

Comment on “Hydrochlorothiazide use and the risk of skin cancer in patients with hypertensive disorder: a nationwide retrospective cohort study from Korea”

“…Nevertheless, we may not expect to see similar risks observed in a European population [2,3] replicated in an Asian population. In fact, in a recent Taiwanese study, hydrochlorothiazide showed no significant association to skin cancer [5]. This may be explained by several factors, including differences in skin phenotype, use of lower hydrochlorothiazide doses, and cultural differences in sun behavior.…”