Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened.
OBJECTIVE
To screen commonly used prescription drugs for possible carcinogenic effects.


METHODS
In a large health care program we identified 105 commonly used drugs, not previously screened. Recipients were followed for up to 12½ years for incident cancer. Nested case-control analyses of 55 cancer sites and all combined included up to ten matched controls per case, with lag of at least 2 years between drug dispensing and cancer. Positive associations entailed a relative risk of 1.50, with p ≤ 0.01 and higher risk for three or more, than for one prescription. Evaluation included further analyses, searches of the literature, and clinical judgment.


RESULTS
There were 101 associations of interest for 61 drugs. Sixty-six associations were judged to have involved substantial confounding. We found evidence that of the remaining 35, the following associations may not be due to chance: sulindac with gallbladder cancer and leukemia, hyoscyamine with nonHodgkin lymphoma, nortriptyline with esophageal and hepatic cancer, oxazepam with lung cancer, both fluoxetine and paroxetine with testicular cancer, hydrochlorothiazide with renal and lip cancer, and nifedipine with lip cancer.


CONCLUSIONS
These preliminary findings suggest that further studies are indicated regarding sulindac, hyoscyamine, nortriptyline, oxazepam, fluoxetine, paroxetine, hydrochlorothiazide, and nifedipine.
Friedman
Gary D
GD
Division of Research, Kaiser Permanente Medical Care Program, 2000 Broadway, Oakland, CA 94612, USA. gdf@dor.kaiser.org
Udaltsova
Natalia
N
Chan
James
J
Quesenberry
Charles P
CP
Habel
Laurel A
LA
D015197:Carcinogenicity Tests / Q000592:standards; D002273:Carcinogens / Q000494:pharmacology; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis* / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D012739:Gonadal Steroid Hormones / Q000097:blood / Q000494:pharmacology; D015658:HIV Infections / Q000453:epidemiology; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D004364:Pharmaceutical Preparations / Q000032:analysis*
D002273:Carcinogens; D012739:Gonadal Steroid Hormones; D004364:Pharmaceutical Preparations