Possible link between hydrochlorothiazide and malignant melanoma


By Will Boggs MD

NEW YORK (Reuters Health) - Long-term hydrochlorothiazide use appears to be associated with an increased risk of malignant melanoma, researchers from Denmark report.

"We have shown in a series of papers that long-term hydrochlorothiazide use is associated with an increased risk of skin cancer, most notably squamous cell carcinoma, and now also potentially with two subtypes of melanoma," Dr. Anton Pottegaard from the University of Southern Denmark, in Odense, told Reuters Health by email. "However, it is important to note that the absolute risk for the individual patient is generally very low."

Dr. Pottegaard's team calculated odds ratios for melanoma associated with cumulative hydrochlorothiazide use, compared with never-use, in their study of 19,273 melanoma cases and 10 times as many population controls.

After adjusting for age, sex, history of nonmelanoma skin cancer and other factors, the odds of developing melanoma were 17% (95% confidence interval, 11% to 23%) higher among individuals who ever used hydrochlorothiazide. For those with cumulative doses of 50,000 mg or more (high-users), the odds were up by 22% (95% CI, 9% to 36%), the researchers report in JAMA Internal Medicine, online May 29.

The absolute risk of melanoma was 2.1% among high-users of hydrochlorothiazide and 1.8% among controls.

There was no clear dose-response pattern between hydrochlorothiazide use and melanoma risk.

Odds ratios for melanoma were higher for nodular melanoma (2.05) and lentigo melanoma (1.61) than for superficial spreading melanoma (1.11).

In contrast, there was no significant association between melanoma risk and long-term use of bendroflumethiazide (another thiazide diuretic), angiotensin-converting enzyme inhibitors, angiotensin-II receptor antagonists, or calcium-channel blockers.

"Pending the results of further studies, physicians and patients might wish to take the present study findings into consideration when choosing antihypertensive treatment, in particular for patients that are at an elevated risk from the outset, e.g., those with immunosuppression, a history of skin cancer, those with fair skin, or patients that are often exposed to the sun," Dr. Pottegaard said. "We fully acknowledge, however, that this aspect must be carefully balanced against other considerations in the complex decision on which antihypertensive to prescribe."

"The implications of the new findings on the overall use of hydrochlorothiazide rest on the authors of the clinical guidelines as well as the regulators," he said.

"An important message for patients using hydrochlorothiazide is that they should not stop taking the drug without consulting their physicians," Dr. Pottegaard added. "We wish to emphasize this point, given the very real dangers of untreated or poorly treated hypertension and the low absolute risk of melanoma observed in our study, the first of its kind."

SOURCE: http://bit.ly/2smC9yQ

JAMA Intern Med 2018.

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