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Long-term aspirin use reduces risk for colorectal cancer
Higher doses needed to produce effect, more research needed to clarify risks

BOSTON - August 23, 2005 - A new report from the Nurses' Health Study finds that regular, long-term aspirin use can significantly reduce the risk of colorectal cancer, as suggested by several earlier studies. However, the benefit appears to require more than a decade and is strongest at dose levels associated with a greater risk of side effects such as bleeding. Similar results were found for non-steroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen and naproxen. The report - from researchers at Massachusetts General Hospital (MGH), Brigham and Women's Hospital and Dana-Farber Cancer Institute - appears in the August 24 Journal of the American Medical Association.

"Several earlier studies have found that, among patients with a history of colon polyps or cancer, regular aspirin treatment prevents the recurrence of precancerous polyps. However, the ability of aspirin to reduce the long-term incidence of invasive cancer has not been well-demonstrated," says Andrew Chan, MD, MPH, of the MGH Gastrointestinal Unit, the paper's lead author. "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."

The Nurses' Health Study (NHS) has followed more than 120,000 female registered nurses since the mid-1970s, asking them to complete a questionnaire on risk factors for and incidence of cancer and cardiovascular disease every two years. In 1980, assessments of diet and the use of aspirin and NSAIDS were added. The current report analyzes information from almost 83,000 NHS participants, among which 962 cases of colorectal cancer were diagnosed during the 20-year study period.

While the incidence of colorectal cancer was lower in the women who took aspirin regularly, the risk reduction was significant only for those taking aspirin 10 years or longer. The benefit increased as dosage levels rose, with the greatest risk reduction seen in those taking more than 14 standard tablets per week. A similar risk reduction was seen with the intake of NSAIDS, with greater benefit also associated with higher dosage; but an analysis of acetaminophen, which is believed to act through different mechanisms, found no association of that medication with colorectal cancer. It is believed that the ability of aspirin and NSAIDS to reduce cancer risk may, at least in part, relate to their shared ability to inactivate the COX-2 enzyme, which could stimulate tumor development.

The risk of serious gastrointestinal bleeding, a known side effect of both aspirin and NSAIDS, also rose as dosage levels increased, with bleeding occurring nearly twice as often in those taking the highest doses. The researchers estimate that a high-dose aspirin regimen that prevented one or two cases of colorectal cancer in a population might also contribute to eight additional cases of serious gastrointestinal bleeding.

"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, particularly compared to other prevention strategies. For now, individuals need to discuss the options with their physicians" says Chan, who is an instructor in Medicine at Harvard Medical School. Chan and his colleagues have already initiated studies aimed to further clarify the impact of long-term use of aspirin and NSAID drugs, particularly in those at high risk for cancer and other chronic diseases.

Additional authors of the study are Charles Fuchs, MD, MPH, senior author, of Dana-Farber Cancer Institute and Brigham and Women's Hospital (BWH); Edward Giovannucci, MD, ScD, Eva Schernhammer, MD, DrPH, and Gary Curhan MD, ScD, all of BWH and the Channing Laboratory at Harvard Medical School; and Jeffrey Meyerhardt, MD, MPH, of Dana-Farber. The study was supported by grants from the National Cancer Institute, the National Institutes of Health, the American Gastroenterological Association and the Foundation for Digestive Health.

The Nurses' Health Study (NHS) was initiated in 1976 at BWH. The NHS is the longest-running, major women's health study ever undertaken and has resulted in hundreds of journal articles, many containing groundbreaking findings on how to prevent some of the major causes of disease and death in women.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $450 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.

Media Contact: Sue McGreevey, MGH Public Affairs

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