Women who took two or more aspirin a week for more than 10 years had a significantly reduced risk of developing colon cancer later in life, according to a study published today.

But the effect is strongest at higher dose levels that may cause side effects like stomach upset and bleeding. The most effective dose is also greater than that typically recommended for people seeking to avoid heart disease.

"Our study did find a protective effect of long-term aspirin use on risk of invasive colorectal cancer, but only at dosage levels considerably higher than those used to prevent cardiovascular disease," said Dr. Andrew Chan, a researcher in the Gastrointestinal Unit at Massachusetts General Hospital and Harvard Medical School and lead author of the study in The Journal of the American Medical Association.

Although several earlier studies had shown that several years of aspirin treatment in patients with a history of colon polyps or cancer can prevent recurrence of those problems, the new research is the first major effort to show that using aspirin and other non-steroidal anti-inflammatory drugs can reduce the incidence of cancer in the longer-term.

The researchers turned to the Nurses Health Study, a three-decade project that has followed risk factors for cancer and heart disease in more than 120,000 female registered nurses, with data updated every two years. Since 1980, the study has also tracked diet and use of pain medications among the women.

The new report analyzed information from nearly 83,000 nurses, among which 982 cases of colorectal cancer were diagnosed over a 20-year period.

Among women who regularly took two or more 325-mg tablets a week, there was a 23 percent reduced risk for colorectal cancer compared with non-regular users. But the benefit clearly increased with the dose: compared to non-users, women who took two to five aspirin a week had an 11 percent reduced risk, but women taking more than 14 aspirin a week had a 32 percent reduced risk.

A similar reduction was seen among women taking other non-steroidal anti-inflammatory drugs, like ibuprofen and naproxen, but not for those taking acetaminophen, which acts through a different mechanism.

Researchers believe that the ability of aspirin and NSAIDs to reduce cancer risk may relate, at least in part, to a shared ability to inactivate the COX-2 enzyme, which can stimulate tumor development.

But taking higher doses of those drugs also raises the risk of serious gastrointestinal bleeding, which occurred nearly twice as often in women taking the highest doses compared with women who said they did not regularly take aspirin.

"Before we can make any recommendations about whether patients should take these medications to reduce their cancer risk, we're going to need additional studies that clarify the risks and benefits of such an approach," Chan said.