Photosensitizing Antihypertensive Agents Linked to Lip Cancer in Non-Hispanic Whites
“In screening pharmaceuticals for possible carcinogenic effects we noted an association between lip cancer risk and the photosensitizing antihypertensive drugs hydrochlorothiazide and nifedipine,” noted Gary D. Friedman, MD, of Stanford University School of Medicine, Stanford, CA, and Kaiser Permanente Medical Care Program, Oakland, CA, and colleagues. “In this study, we further characterized the risk of lip cancer associated with these and other commonly used antihypertensive drugs.”
They noted that “lip cancer includes malignant neoplasms of the vermilion border, commissure, and labial mucosa, but excludes cancers originating on the skin of the lip. The histologic type is predominantly squamous cell, and most lesions occur on the lower lip.”
Between August 1, 1994 and February 29, 2008, 712 non-Hispanic white patients were identified with lip cancer; 22,904 controls were matched for age, sex, and cohort year. “We determined use, at least 2 years before diagnosis or control index date, of the commonly prescribed diuretics hydrochlorothiazide and hydrochlorothiazide combined with triamterene, the angiotensin converting enzyme inhibitor lisinopril, the calcium channel blocker nifedipine, and the alpha-adrenergic blocker atenolol, the only nonphotosensitizer agent studied. We analyzed the use of each drug exclusively and regardless of use of the others, and focused on duration of use,” the investigators wrote.
Compared with no use, at least a 5-year supply of a drug resulted in the following odds ratios hydrochlorothiazide, 4.22 (95% CI 2.82–6.31); hydrochlorothiazide-triamterene, 2.82 (1.74–4.55); lisinopril, 1.42 (0.95–2.13); nifedipine, 2.50 (1.29–4.84); and atenolol, 1.93 (1.29–2.91). “When the other drugs were excluded, the odds ratio for atenolol was reduced to 0.54 (0.07-4.08),” they noted. The study controlled for cigarette smoking, also a known risk factor for lip cancer.
“Lip cancer remains rare and an increased risk of developing it is generally outweighed by the benefits of these blood pressure drugs and other photosensitizing medications,” said Dr. Friedman. “Physicians prescribing photosensitizing drugs should ascertain whether patients are at high risk of lip cancer by virtue of fair skin and long-term sun exposure and discuss lip protection with them. Although not yet confirmed by clinical trials, likely preventive measures are simple: a hat with sufficiently wide brim to shade the lips and lip sunscreens.”