Antihypertensives associated with increased lip cancer risk

Antihypertensive drugs are linked to an increased risk for lip cancer, a new study has found.

Researchers used data from the Kaiser Permanente Medical Care Program in northern California to examine whether an association existed between antihypertensive drugs, many of which are photosensitizing, and lip cancer. Data on cancer incidence and antihypertensive prescriptions dispensed between Aug. 1, 1994 and Feb. 29, 2008 were evaluated, and patients with lip cancer were matched with controls by age, sex and year of cohort entry.

Hydrochlorothiazide, triamterene, lisinopril, and nifedipine are photosensitizing drugs, while atenolol is not. The authors determined use of hydrochlorothiazide (with or without triamterene), lisinopril, nifedipine and atenolol two or more years before lip cancer diagnosis or the control index date and evaluated any association, focusing on duration of therapy. Matched case-control sets were analyzed using logistic regression while controlling for cigarette smoking.

The study results were published online Aug. 6 by Archives of Internal Medicine.

Overall, a total of 712 patients with lip cancer and 22,904 controls were included in the study. Approximately three-quarters of participants were men. Patients who had received an organ transplant, patients who had HIV infection, and patients who were not of non-Hispanic white ethnicity were excluded.

Compared with no use of antihypertensive therapy, odds ratios for developing lip cancer after five years of being prescribed a specific antihypertensive drug (taken with or without other antihypertensive agents) were 4.22 (95% confidence interval [CI], 2.82 to 6.31) for hydrochlorothiazide, 2.82 (95% CI, 1.74 to 4.55) for hydrochlorothiazide-triamterene, 1.42 (95% CI, 0.95 to 2.13) for lisinopril, 2.50 (95% CI, 1.29 to 4.84) for nifedipine, and 1.93 (95% CI, 1.29 to 2.91) for atenolol.

The authors performed a separate analysis of patients who received atenolol, excluding individuals who had received any of the other drugs, and found an odds ratio of 0.54 (95% CI, 0.07 to 4.08) for at least five years of exposure, which is consistent with its lack of photosensitizing properties. Risk seemed to increase with duration of use for hydrochlorothiazide, hydrochlorothiazide-triamterene, and nifedipine, while the risk with lisinopril appeared to be highest at one to five years of use. In multivariable analysis adjusted and unadjusted for cigarette smoking, use of hydrochlorothiazide, hydrochlorothiazide-triamterene, and nifedipine remained statistically significantly associated with lip cancer, while lisinopril's association was no longer statistically significant.

The authors acknowledged that they were not able to adjust for sun exposure, and that the database used in their study did not allow analysis of lip cancer risk by histological type (basal-cell, squamous-cell, or melanoma), among other limitations. They also stressed that their results do not establish a causal relationship and they called for further studies to confirm their findings.

However, they concluded that physicians who prescribe photosensitizing drugs should determine their patients' existing risk for lip cancer and make them aware of the importance of lip protection.

“Although not confirmed by clinical trials, likely preventive measures are simple: a hat with a sufficiently wide brim to shade the lips and lip sunscreens,” they wrote.