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Updated: Jun 21, 2026

High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)
Published on: May 10, 2016
Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously
Gary D Friedman1, Natalia Udaltsova, James Chan
1Division of Research, Kaiser Permanente Medical Care Program, 2000 Broadway, Oakland, CA 94612, USA. gdf@dor.kaiser.org
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.
Insights
This study screened 105 common prescription drugs for cancer risk. Preliminary findings suggest potential links between specific drugs, including sulindac and hydrochlorothiazide, and various cancers, warranting further investigation.
Area of Science:
- Pharmacovigilance
- Oncology
- Epidemiology
Background:
- Prescription drug use is widespread.
- The carcinogenic potential of many commonly prescribed medications remains unevaluated.
- Identifying drug-associated cancer risks is crucial for public health.
Purpose of the Study:
- To screen a cohort of 105 commonly used prescription drugs for potential carcinogenic effects.
- To identify specific drugs associated with an increased risk of developing various cancers.
- To provide preliminary evidence for further investigation into drug-induced carcinogenesis.
Main Methods:
- A nested case-control study design was employed within a large healthcare program.
- 105 frequently prescribed drugs were screened for associations with 55 cancer sites.
- Follow-up extended up to 12.5 years, with a minimum 2-year lag between drug dispensing and cancer diagnosis.
Main Results:
- 101 drug-cancer associations were identified for 61 drugs.
- After adjusting for confounding factors, 35 associations remained significant.
- Potential links include sulindac (gallbladder cancer, leukemia), hydrochlorothiazide (renal, lip cancer), and others with specific cancers.
Conclusions:
- Preliminary evidence suggests potential carcinogenic risks for sulindac, hyoscyamine, nortriptyline, oxazepam, fluoxetine, paroxetine, hydrochlorothiazide, and nifedipine.
- Further research is warranted to confirm these drug-cancer associations.
- These findings highlight the importance of ongoing drug safety surveillance.
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