Antihypertensive drugs and lip cancer in non-Hispanic whites

Arch Intern Med. 2012 Sep 10;172(16):1246-51. doi: 10.1001/archinternmed.2012.2754.


Background: In screening pharmaceuticals for possible carcinogenic effects we noted an association between lip cancer risk and the photosensitizing antihypertensive drugs hydrochlorothiazide and nifedipine. In this study, we further characterized the risk of lip cancer associated with these and other commonly used antihypertensive drugs.

Methods: In a comprehensive medical care program, we evaluated prescriptions dispensed and cancer occurrence from August 1, 1994, to February 29, 2008. We identified 712 patients with lip cancer (cases) and 22,904 comparison individuals (controls) matched for age, sex, and cohort year of entry in the susceptible group, non-Hispanic whites. 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 β-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. Conditional logistic regression was used for analysis of matched case-control sets, with control for cigarette smoking.

Results: At least a 5-year supply of a drug yielded the following odds ratios (95% CIs), respectively, compared with no use: hydrochlorothiazide, 4.22 (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).

Conclusion: These data support an increased risk of lip cancer in non-Hispanic whites receiving treatment for hypertension with long-term use of photosensitizing drugs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / adverse effects*
  • Antihypertensive Agents / therapeutic use
  • Female
  • Humans
  • Hydrochlorothiazide / adverse effects*
  • Hydrochlorothiazide / therapeutic use
  • Hypertension / drug therapy
  • Lip Neoplasms / chemically induced*
  • Male
  • Middle Aged
  • Nifedipine / adverse effects*
  • Nifedipine / therapeutic use
  • Risk
  • White People*


  • Antihypertensive Agents
  • Hydrochlorothiazide
  • Nifedipine