New research shows chronic users of acetaminophen, a top-selling painkiller known as Tylenol in the U.S. and paracetamol in Europe, are at slightly increased risk for blood cancers.
Yet the risk remains low, and it's still uncertain what role the drug plays.
The finding adds another twist to the complicated evidence linking cancer and painkillers, and hints acetaminophen might be different from the rest.
Earlier work has shown that aspirin use might lower the odds of dying from colon cancer but increase the risk of bleeding ulcers. The picture has been less clear for blood, or hematologic, cancers, however.
"Prior to this study there was very little evidence that aspirin reduces your risk of hematological cancers," said Emily White of the Fred Hutchinson Cancer Research Center in Seattle, who worked on the new research.
There were some suggestions that acetaminophen might increase the risk of the cancers, on the other hand, but those were based on individual cases of blood cancer.
Studies of individual patients aren't considered as strong as the new one, which tracked a large population of healthy people over time.
"We have the first prospective study," White told Reuters Health.
Still, she warned, there is no proof that acetaminophen causes cancer, and the new results need to be confirmed before they are used in any treatment decision.
Earlier work has linked acetaminophen to asthma and eczema as well, but scientists still don't agree on whether the drug is the actual culprit or just an innocent bystander.
The new study suffers from the same limitations, in that people who use lots of painkillers could be dealing with medical problems that set them up for cancer down the road.
The scientists followed nearly 65,000 older men and women in Washington State. At the outset, they asked the participants about their use of painkillers over the past ten years and made sure that no one had cancer (except skin cancer).
Over some six years on average, 577 people -- or less than one percent -- developed a cancer involving the blood cells.
Examples of such cancers include lymphoma and myelodysplastic syndrome, or MDS.
More than nine percent of people who developed one of these cancers used high amounts of acetaminophen, compared to only five percent of those who didn't get sick.
After accounting for things like age, arthritis and a family history of certain blood cancers, chronic acetaminophen users had nearly twice the risk of developing the disease.
"A person who is age 50 or older has about a one-percent risk in ten years of getting one of these cancers," White said. "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 two percent."
No other painkillers -- including aspirin and ibuprofen -- were tied to the risk of blood cancers.
Dr. Raymond DuBois, a cancer prevention expert at the University of Texas MD Anderson Cancer Center in Houston, said acetaminophen works very differently than other painkillers and so might be expected to have different effects on cancer.
Still, "It was quite surprising to see that acetaminophen use increased the risk of" blood cancers, DuBois, who was not involved in the study, told Reuters Health by email.
McNeil Consumer Healthcare, the Johnson & Johnson subsidiary that sells Tylenol, did not respond to requests for comment.
White said it is too soon to make any recommendations based on the new study, and that none of the painkillers is free of side effects.
"Long-term use of any over the counter drug might have adverse effects," she said. "You have to weigh the benefits against the risk of all the drugs."