Thiazide use may increase risk of skin cancers: BMC

Taiwan: Hydrochlorothiazide is associated with an increased risk for non-melanoma skin cancer (NMSC), especially squamous cell carcinoma (SCC) and melanoma, whereas bendroflumethiazide and indapamide are not associated with a significant risk for skin cancers, states an article published in BMC Medicine.

Globally, nearly 2 and 3 million non-melanoma skin cancers and 132,000, melanoma skin cancers occur yearly. Identification and avoidance of modifiable risk factors may mitigate this increasing trend. One of the risk factors is the interaction of sunlight with medications, leading to photosensitivity responses in susceptible patients, potentially increasing the risk of skin cancer. Thiazide diuretics, first-line antihypertensives, have photosensitizing properties with a biologically plausible causal association with skin cancers. Previous findings on the associations of thiazide use with skin cancers were conflicting.

Shih-Chieh Shao, National Cheng Kung University, Taiwan, and colleagues conducted a study to examine the associations of individual thiazide use with skin cancer risk, differentiated by subtypes of skin cancers, geographic regions, and cumulative doses of individual thiazides.

Researchers searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for relevant studies, scanned the references of included studies, and consulted experts. They included case-control and cohort studies or randomized trials reporting the associations of individual thiazide or thiazide-like diuretics use with skin cancers. Non-melanoma skin cancer (NMSC) and melanoma were analyzed separately.

A random-effects model meta-analysis was conducted for pooled odds ratio (OR) and hazard ratio (HR) for skin cancers related to individual thiazide use. Researchers included 15, 5, and 5 case-control or cohort studies reporting the risk for skin cancers associated with hydrochlorothiazide, bendroflumethiazide, and indapamide use, respectively, with 17,848,313 participants.

Key findings of the study,

• Hydrochlorothiazide use increased the risk of NMSC (HR 1.26), SCC(HR 1.61), and melanoma (HR 1.03).

• The increased risks for SCC were associated with high cumulative doses of hydrochlorothiazide (HR 1.20).

• Hydrochlorothiazide use was associated with different subtypes of melanoma including superficial spreading, nodular and lentigo maligna melanoma.

• Various cumulative doses of hydrochlorothiazide were associated with increased odds of melanoma.

• The association of hydrochlorothiazide use with increased risk of NMSC and melanoma only appeared in non-Asian countries.

• No meaningful increase in the risk for skin cancers was associated with bendroflumethiazide and indapamide.

The authors conclude that there is an increased risk for SCC and melanoma among patients receiving hydrochlorothiazide, but no significant or clinically meaningful risk for those receiving bendroflumethiazide or indapamide. Healthcare professionals and patients should be made aware of the different risk profiles of skin cancers associated with different thiazides, cumulative doses, and regions.

The authors recommend dermatology consultation and optimal photo-protection for hydrochlorothiazide users.

Reference:

Shao, SC., Lai, CC., Chen, YH. et al. Associations of thiazide use with skin cancers: a systematic review and meta-analysis. BMC Med 20, 228 (2022). https://doi.org/10.1186/s12916-022-02419-9