Some Antihypertensives May Raise Lip Cancer Risk
Abstract & Commentary
By Rahul Gupta, MD, MPH, FACP. Clinical Assistant Professor, West Virginia University School of Medicine, Charleston, WV. Dr. Gupta reports no financial relationships relevant to this field of study.
Synopsis: Several commonly used photosensitizing antihypertensive drugs can confer as much as a four-fold increase in the risk of lip cancer when prescribed long-term in non-Hispanic whites.
Source: Friedman GD, et al. Antihypertensive drugs and lip cancer in non-hispanic whites. Arch Intern Med 2012;172:1246-1251.
Hypertension is a serious public health challenge in the united States, affecting approximately one in three U.S. adults, an estimated 68 million. It is a major risk factor for heart disease, stroke, congestive heart failure, and kidney disease, which are among the leading causes of death in the United States. In 2010, hypertension was projected to cost the United States $93.5 billion in health care services, medications, and missed days of work. As more Americans become aware of their condition and visit their primary care physician, they are often placed on prescription therapy to control the disorder. The benefits of antihypertensive drugs for the reduction of cardiovascular morbidity and mortality are well established. However, not all studies have demonstrated similar benefits in total mortality.1 This can be explained by possibly having an increase in the non-cardiovascular mortality in the treated hypertensive patients. Since several antihypertensive agents have been implicated in the increase of incidence and mortality among treated hypertensive patients, it can be hypothesized that the treated hypertensive patients may die of malignancies in greater proportions than those not on these medications.2 Therefore, it makes sense to ensure that when we prescribe antihypertensive drugs to our patients, there is either no or an acceptable risk from adverse events. In earlier research when screening drugs for possible carcinogenic effects, the investigators observed an association between the risk for lip cancer and use of the photosensitizing antihypertensive agents hydrochlorothiazide and nifedipine.3 Because sun exposure is a known risk factor for lip cancer, a causal relationship between photosensitizing drugs and lip cancer risk is biologically feasible.
In their study, Friedman et al conducted a case-control study utilizing a large cohort from the Kaiser Permanente System. They reviewed more than 13 years (August 1994 through February 2008) of pharmacy records and identified 712 cases of lip cancer among non-Hispanic whites who were not HIV-positive or organ transplant recipients at diagnosis. They compared these cases with 22,904 matched controls without lip cancer. The five commonly used drugs studied included photosensitizers lisinopril, nifedipine, and hydrochlorothiazide alone or in combination with triamterene, as well as the non-photosensitizer atenolol.
The researchers found that the commonly used photosensitizing antihypertensive drugs hydrochlorothiazide, hydrochlorothiazide-triamterene, and nifedipine were associated with an increased risk of lip cancer. For these agents, among those patients who were dispensed at least a 5-year supply of a drug yielded the following odds ratios (OR) (95% confidence intervals [CI]), respectively, compared with no use: hydrochlorothiazide (OR 4.22, CI 2.82-6.31); hydrochlorothiazide-triamterene (OR 2.82, CI 1.74-4.55); lisinopril (OR 1.42, CI 0.95-2.13); and nifedipine (OR 2.50, CI 1.29-4.84). Atenolol, when used alone, was not associated with increased risk, and findings for lisinopril were equivocal. Nearly all malignancies were of squamous cell type and the risk seemed to correlate with increasing duration of use.
Commentary
While antihypertensive agents are commonly prescribed, the photosensitizing nature of several of these drugs is not well known to physicians and patients alike. The current study by Friedman et al demonstrates that several commonly used photosensitizing antihypertensive drugs increase the risk for lip cancer by two- to four-fold. Though the researchers were unable to adjust for sun exposure, the most important lip cancer risk factor, it is unlikely that users of the antihypertensive drugs associated with lip cancer experience additional sun exposure than nonusers. This study helps to remind us that even when an increased risk of a rare disease development (such as lip cancer) is generally outweighed by the benefits of drugs, there is still a value to understanding the risks. Only by being aware of the risks in this circumstance can it be recommended that physicians prescribing photosensitizing drugs should ascertain whether patients are at high risk of lip cancer because of their fair skin and long-term sun exposure and, therefore, discuss lip protection with them. Since it is also likely that patients receiving these agents may be at similar increased risk of other cancers of the skin (basal cell and squamous cell), simple interventions such as using lip balm; wearing sun protective clothing, including hats, sunglasses, and sunscreens; and avoiding being outside during times of the day when the sun is most intense are likely to protect patients from damaging ultraviolet radiation, regardless of whether they are receiving a photosensitizing agent. Not only is this good medical practice, but it also is a good public health intervention.
References
1. Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: Results of prospectively-designed overviews of randomized trials. Lancet 2003;362:1527-1535.
2. Sipahi I, et al. Meta-analysis of randomized controlled trials on effect of angiotensin-converting enzyme inhibitors on cancer risk. Am J Cardiol 2011;108:294-301.
3. Friedman GD, et al. Screening pharmaceuticals for possible carcinogenic effects: Initial positive results for drugs not previously screened. Cancer Causes Control 2009;20:1821-1835.
Several commonly used photosensitizing antihypertensive drugs can confer as much as a four-fold increase in the risk of lip cancer when prescribed long-term in non-Hispanic whites.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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