Association Between the Use of Thiazide Diuretics and the Risk of Skin Cancers: A Meta-Analysis of Observational Studies

Abstract

BackgroundThiazide diuretics are among the most widely prescribed antihypertensive agents. Given their photosensitizing effects, however, there are concerns that they may increase the risk of skin cancers. In this meta-analysis, we investigated an association between the use of thiazide diuretics and the risk of skin cancers.MethodsWe identified studies by searching three electronic databases (PubMed, EMBASE, and the Cochrane Library) from their inception to October 30, 2017. Nine relevant observational studies (seven case-control and two cohort studies) were included in this study. Since included studies were unlikely to be functionally equal, pooled estimates were calculated using random-effects meta-analysis.ResultsThe use of thiazide diuretics was associated with an increased risk of squamous cell carcinoma (adjusted odds ratio (aOR), 1.86; 95% confidence interval (CI), 1.23 - 2.80) and marginally increased risk of basal cell carcinoma (aOR, 1.19; 95% CI, 1.02 - 1.38) and malignant melanoma (aOR, 1.14; 95% CI, 1.01 - 1.29). In the subgroup analysis, hydrochlorothiazide or hydrochlorothiazide combination medications were significantly associated with squamous cell carcinoma without significant heterogeneity among studies (aOR, 2.04; 95% CI, 1.79 - 2.33; Higgin’s I2 value = 0.0 %; Q-statistics = 2.7, P value = 0.445).ConclusionsOur results suggested that the use of thiazide diuretics may be associated with an increased risk of skin cancers. This association was most prominent between the use of hydrochlorothiazide or hydrochlorothiazide combination medications and the risk of squamous cell carcinoma. Further studies are needed to confirm these findings.

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

“…Thiazide diuretics are known to possess photosensitising properties 7 ; in 2013, the International Agency for Research on Cancer classified HCTZ as “possibly carcinogenic to humans” (Group 2B) 8 . Recent studies reported HCTZ increased the risk of developing a range of skin cancers, particularly squamous cell carcinomas (SCCs), 2,7,9‐13 and warnings from medicines regulatory agencies in Europe, 14 the UK, 15 Canada, 16 Singapore 17 and New Zealand 18 followed from October 2018. These findings and regulatory warnings are particularly relevant for Australia, which has the highest incidence of skin cancer in the world 19…”

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“…Another study showed a possible association between labial squamous cell carcinoma and the exposure to this thiazide, in 633 cases compared to 63,067 controls, with a cumulative dose-response relationship with adjusted OR of 2.1 (95% CI : 1.7-2.6) which increased up to OR 3.9 (3.0-4.9) for patients who used it at high dose (~ 25.000 mg) and a OR 7.7 (5.7-10.5) for the highest cumulative dose (~ 100,000 mg) [33]. Finally, a recent study, conducted with the evaluation of different databases (PubMed, EMBASE, Cochrane Library), would confirm the association with increased risk of skin cancers, especially squamous cell carcinoma (underlining the need for further studies to confirm the results) [34]. The AIFA report concluded the report by inviting the physicians to the following prescriptive behaviors and to adopt the following precautions: information on the risk of non-melanoma skin cancers for patients taking hydrochlorothiazide, alone or in combination with other drugs, with the regular control and self-control of the skin for the early identification of any new lesions or changes to existing lesions, with notification to your doctor of any suspected skin lesion; examination of suspected skin lesions both from a clinical but also histological point of view, using the bioptic exam; warning patients about the limitation of exposure to sunlight/UV rays, with the use of adequate protection when exposed to sunlight/UV rays, to minimize the risk of skin cancers; careful evaluation and discernment on the prescription/use of hydrochlorothiazide in patients who have had a previous skin cancer.…”

Recent Warnings about Antihypertensive Drugs and Cancer Risk: Where Do They Come From?

“…37 The recent north European nationwide case control study by Pedersen et al found a clear doseresponse relationship between hydrochlorothiazide use and both BCC and SCC, especially the latter cancer type. 5 In this analysis, the use of high 39 It must be pointed out that this analysis is based on few and generally heterogeneous observational studies for every type of skin cancer and many of these studies do not consider the interaction between different skin types, sun exposure and family history of skin cancer. Despite this, the association between thiazide diuretics and SCC risk appears to be supported by the epidemiological evidence available to date.…”