Cancer risk associated with long-term use of acetaminophen in the prospective VITamins and lifestyle (VITAL) study.

BACKGROUND Acetaminophen (paracetamol) is a widely used over-the-counter drug, but concerns of genotoxic effects have been raised. After we recently found an almost two-fold increased risk of hematologic malignancies associated with high use of acetaminophen in the prospective VITamins And Lifestyle (VITAL) study, we herein further examined the association between acetaminophen use and cancer risk in the VITAL cohort. METHODS A total of 62,841 men and women aged 50 to 76 years were recruited from 2000 to 2002, and incident malignancies other than nonmelanoma skin cancer (n = 5,750) were identified through December 2008 via linkage to the Surveillance, Epidemiology, and End Results cancer registry. HRs associated with acetaminophen use for incidence of total cancers and nonhematologic cancer subcategories were estimated with Cox proportional hazards models that were adjusted for age, demographics, cancer risk factors, and medical conditions that may be indications for acetaminophen use. RESULTS Use of acetaminophen was not associated with total cancer risk. We also observed no associations for most major nonhematologic cancer sites, including cancers of the gastrointestinal system, lung, urinary tract, skin, prostate, or female organs. CONCLUSION This study failed to provide evidence of an association between acetaminophen use and total cancer risk or incidence of nonhematologic malignancies. IMPACT Together with our previous findings, the analyses from the VITAL study suggest a particular sensitivity of the hematopoietic system to the mutagenic effects of acetaminophen.