Some high blood pressure medicines, when taken long term, may increase the risk of lip cancer in white people, according to new research.

The list includes commonly used drugs such as the diuretic hydrochlorothiazide (HydroDIURIL, Microzide, others) and the ACE inhibitor lisinopril (Prinivil, Zestril).

The finding, however, is buffered with some reassurance. "I want to emphasize that lip cancer is rare," says Gary D. Friedman, MD, an emeritus researcher and former director of the Kaiser Permanente Northern California Division of Research. He led the study.

Lip cancer rarely spreads, he says. It is usually recognized early and treated promptly.

"I do not want to alarm people to the extent they are going to stop taking their medicine for blood pressure," he says. The study findings are not a reason to stop any medicines that make people more sensitive to the sun, he says.

The study is published online in the Archives of Internal Medicine.

Every year in the U.S., about 35,000 people are diagnosed with oral cancers, including lip cancers, according to the National Cancer Institute.
Blood Pressure Drugs & Lip Cancer: Study Details

In a previous study, Friedman had noticed an increase in lip cancers among people on certain high blood pressure medicines.

For this study, he evaluated the types of blood pressure prescriptions dispensed and lip cancers found in patients at Kaiser Permanente from 1994 until early 2008.

He focused only on lip cancers, Friedman says, because data on skin cancers was not available.

Friedman focused on five high blood pressure drugs or drug combinations that are commonly prescribed. Besides hydrochlorothiazide and lisinopril, they included:

    Hydrochlorothiazide-triamterene (Dyazide, Maxzide)
    Nifedipine (Adalat, Nifediac, Procardia, others)
    Atenolol (Senormin, Tenormin)

All but atenolol are known to make the skin more sun-sensitive.
Blood Pressure Drugs & Lip Cancers: Results

During the study, 712 patients on blood pressure drugs were diagnosed with lip cancer. The researchers compared them to nearly 23,000 others who did not have lip cancer.

After finding a reduced risk of lip cancer among all minority groups, Friedman only evaluated white people.

For those who took the drugs for five years or longer, the risk compared to those who didn't take blood pressure drugs varied by drug.

    Those on hydrochlorothiazide had more than four times the risk.
    Those on hydrochlorothiazide-triamterene had a nearly three times greater risk.
    Those on nifedipine, 2.5 times higher risk.
    Those on lisinopril, 1.4 times greater risk.

The findings for lisinopril were more uncertain than for some other drugs, Friedman says. When taken alone, atenolol was not linked with an increased risk of lip cancer.

The average age at diagnosis was 68. Most people had a cancer type known as squamous cell.

Cigarette smoking, a known risk factor for oral cancers, further boosted risk for lip cancer, Friedman says.

"Cigarette smokers had about a 1.5-fold increased risk," he says.

No information was available on occupations or on sun exposure.

The findings would most probably extend to skin cancers elsewhere, he says. Other research has shown a link, he says. This type of study, too, can only show a link, not cause and effect.

Friedman suggests wearing a hat wide brimmed enough to shade the lips. Lip balms and lipsticks often contain sunscreen.

Among other medicines that make people more sensitive to the sun, he says, are certain antidepressants, nonsteroidal anti-inflammatory drugs, and antibiotics.

The National Cancer Institute supported the study. Friedman has consulted for Allergan, but the company had no role in the current study.
High Blood Pressure Drugs & Lip Cancer: Second Opinion

"It's certainly an important link if it is real," says Peter Galier, MD, an internal medicine specialist at UCLA Medical Center, Santa Monica. He reviewed the findings.

Other research needs to verify it, says Galier, an associate professor of medicine at the University of California, Los Angeles, David Geffen School of Medicine.

Until that is done, he says, one message would be to "protect your lips as you protect your face."

"Another big message is, if you are on these drugs please stop smoking, because your risk of lip cancer skyrockets."