High use of acetaminophen, a high-selling over-the-counter analgesic known in Europe as paracetamol and more commonly in the US as the brand Tylenol, is linked to an almost two-fold increased risk of certain blood cancers, although no such link was found for aspirin, non-aspirin NSAIDs (nonsteroidal anti-inflammatory drugs), or ibuprofen, according to according to a large new study from the US, published online this week in the Journal of Clinical Oncology.

Although the researchers found that prolonged high use of acetaminophen (4 or more times per week for four years or more) nearly doubled the risk of certain cancers involving the blood cells (such as lymphoma and myelodysplastic syndrome, or MDS), the risk is still small.

The study sheds no light, however, on mechanisms linking acetaminophen to the development of blood cancers, if there are any.

The researchers found no link between high use acetaminophen and another group of blood cancers called chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Co-author Emily White, member of the Fred Hutchinson Cancer Research Center, and Professor of Epidemiology, School of Public Health at the University of Washington in Seattle, said the risk of a person aged 50 or over getting one of the blood cancers is about 1% in ten years.

“Our study suggests that if you use acetaminophen at least four times a week for at least four years, that would increase the risk to about 2%,” said White, according to a Reuters news agency report.

White and colleagues wrote in their background information that previous studies disagree about whether NSAIDs are linked to “incident hematologic malignancies” or certain types of blood cancer, but tended to agree that there is an increased risk from acetaminophen (paracetamol).

So the researchers decided to take a closer look by examining data from a large prospective cohort study, the Vitamins and Lifestyle (VITAL) study.

From the VITAL study they got demographic, health and history data including daily use of analgesics of 64,839 men and women between 50 and 76 years of age who enrolled between 2000 and 2002. From the Surveillance, Epidemiology and End Results cancer registry they got data on blood cancer incidence in the group and found 577 incident hematologic malignancies through to December 2008.

They used statistical tools like Cox proportional hazards models to look for links between use of analgesics and blood cancers, and adjusted the results for the usual confounders such as age, gender, race/ethnicity, education, smoking, general health (self-rated), various types of pain, fatigue, and also family history of blood cancers such as leukemia/lymphoma.

The researchers defined “high use of acetaminophen/paracetamol” as taking it on 4 days a week or more for at least 4 years.

The adjusted results showed that:

  • There was an increased risk of incident hematologic malignancies associated with high use of acetaminophen.
  • The statistical analysis showed this to be a Hazard Ratio (HR) of 1.84, with a 95% Confidence Interval (CI) ranging from 1.35 to 2.50 with P trend=0.004.
  • The link was evident for myeloid neoplasms, non-Hodgkin’s lymphomas, and plasma cell disorders, but not for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
  • The statistics showed these links to be: HR for myeloid neoplasms = 2.26 (95% CI ranging from 1.24 to 4.12); HR for non- Hodgkin’s lymphomas = 1.81(95% CI from 1.12 to 2.93), HR for plasma cell disorders = 2.42 (95% CI from 1.08 to 5.41), and HR for CLL/SLL = 0.84 (95% CI from 0.31 to 2.28).
  • Increasing use of aspirin, nonaspirin NSAIDs, or ibuprofen did not appear to affect the risk of incident hematologic malignancies either way.

The researchers concluded that:

“High use of acetaminophen was associated with an almost two-fold increased risk of incident hematologic malignancies other than CLL/SLL.”

They also noted that:

“Neither aspirin nor nonaspirin NSAIDs are likely useful for prevention of hematologic malignancies.”

Some studies have suggested that aspirin increases the risk of bleeding ulcers, while others say it increases the chances of surviving colon cancer.

White said while they could not make any recommendations based on their findings, she warned people to be wary of long term use of any over the counter drug: they all have their various side effects, and people should always weigh the benefits against the risks.

“Long-Term Use of Acetaminophen, Aspirin, and Other Nonsteroidal Anti-Inflammatory Drugs and Risk of Hematologic Malignancies: Results From the Prospective Vitamins and Lifestyle (VITAL) Study.”
Roland B. Walter, Filippo Milano, Theodore M. Brasky, and Emily White.
Journal of Clinical Oncology, published online 9 May 2011.
DOI:10.1200/JCO.2011.34.6346.

Written by: Catharine Paddock, PhD