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

Abstract

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.

Use of Hydrochlorothiazide and Risk of Melanoma and Nonmelanoma Skin Cancer

“…For melanoma skin cancer, previous case-control studies from Denmark comparing hydrochlorothiazide with non-use found moderate associations for both ever-use (IRR 1.32, 95% CI 1.03-1.70 and OR 1.17, 95% CI 1.11-1.23, respectively) [11,12], and high use (≥ 50,000 mg) (OR 1.22, 95% CI 1.09-1.36) [12]. In contrast, two nested case-control studies from Australia and the UK reported small to no association with hydrochlorothiazide for both ever-use and high use (≥ 25,000 mg and ≥ 50,000 mg, respectively) of hydrochlorothiazide, when compared with non-use [10,26].…”

Telmisartan/hydrochlorothiazide-induced nevus-associated cutaneous melanoma: first report in the medical literature

“…[7,8], are also supported by a number of entirely clinical observations [2,3,9,10]. These three indisputable circumstances should lead to a serious rethinking of the risks, not only of monotherapy of hypertension with angiotensin receptor blockers, but also of the combination with thiazide diuretics, which have different pathophysiological but ultimately similar effects to melanocytes, in that they are also able to potentiate carcinogenesis or the transition of nevi to cutaneous melanoma [2,[4][5][6]10]. This potentiation by thiazide diuretics occurs by a different molecular mechanism than that described for the angiotensin receptor blockers/sartans, as they increase patients' photosensitivity to UV radiation, thereby indirectly potentiating the risk of mutations in the p53 and CDKN2A cell cycle regulators -eventually leading to persistent UV damage [17,18].…”

“…The situation is similar with thiazide diuretics, for which the development of non-melanoma skin cancer has recently been added as a possible side effect in medical leaflets. Furthermore, according to a number of scientific papers, the incidence of melanoma following their use is defined as real and growing in frequency [4][5][6].…”

Use of hydrochlorothiazide and risk of skin cancer in a large nested case‐control study in Spain

“…However, most findings were not directly comparable mainly due to differences in the study methods used and study‐specific limitations. Recently, several studies have found an increased risk of skin and lip cancer related to high cumulative doses of hydrochlorothiazide (HCTZ) in populations from Denmark, 7–9 Iceland, 10 United Kindom 11–13 and Australia, 14 but not in a population from Taiwan 15 …”