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Hydrochlorothiazide use may increase melanoma risk

Patients classified as high users of hydrochlorothiazide had a higher risk for melanoma, according to findings published in JAMA Internal Medicine.

“We have recently shown that hydrochlorothiazide use increases the risk of lip and nonmelanoma skin cancer, notably squamous cell carcinoma,” Anton Pottegård, MScPharm, PhD, from the University of Southern Denmark, and colleagues wrote. “It would have substantial implications if the carcinogenic effect of hydrochlorothiazide also extended to malignant melanoma.”

Pottegård and colleagues identified 19,273 verified cases of melanoma and matched each to 10 cancer-free controls (n = 192,730) to determine if hydrochlorothiazide increases the risk for melanoma.

High use of hydrochlorothiazide, defined as 50,000 mg or more, was prevalent in 2.1% of cases and 1.8% of controls and was associated with an increased risk for melanoma (adjusted OR = 1.22; 95% CI, 1.09-1.36). A dose-response pattern between use of hydrochlorothiazide and melanoma risk was not found. Results remained after accounting for melanoma localization, stage, age, sex and history of nonmelanoma skin cancer.

The odds of melanoma were higher for nodular melanoma (8.8% of cases; OR = 2.05; 95% CI, 1.54-2.72) and lentigo melanoma (2.6% of cases; OR = 1.61; 95% CI, 1.03-2.5) than for superficial spreading melanoma (72% of cases; OR = 1.11; 95% CI, 0.97-1.27).

Long-term use of bendroflumethiazide (OR = 1.1; 95% CI, 1.02-1.19), angiotensin-converting enzyme inhibitors (OR = 1.07; 95% CI, 0.99-1.16), angiotensin-II receptor antagonists (OR = 1.18; 95% CI, 1.07-1.29) and calcium-channel blockers (OR = 1.06; 95% CI, 0.97-1.14) demonstrated null associations for melanoma risk.

“The findings for melanoma subtype are somewhat surprising, as lentigo and superficial spreading melanoma are known to be associated with high sun exposure, whereas the etiology of nodular melanomas is less elucidated,” Pottegård and colleagues concluded. “It is worrying that hydrochlorothiazide use appears to be associated with an increased risk of melanoma, and the particular associations observed for lentigo melanoma and nodular melanoma warrant further research.” – by Alaina Tedesco

Disclosure: Pottegård reports receiving grants from LEO Pharma. Please see study for all other authors’ relevant financial disclosures.