BOSTON - March 15, 2005 - The association between regular aspirin use and a reduced risk of precancerous colon polyps may be strongest in those with particular genetic variants. In the March 16 Journal of the National Cancer Institute, researchers report that aspirin use appears to reduce the incidence of colon polyps more strongly in women with alternative forms of a gene involved in the metabolism of aspirin than in those with the most common form of the gene. The report - from researchers at Massachusetts General Hospital (MGH), Brigham and Women's Hospital (BWH) and Dana-Farber Cancer Institute (DFCI) - analyzes data from the Nurse's Health Study.
"Several studies by our group and others have suggested that aspirin may help prevent colon polyps, but since aspirin therapy also has risks, it would be helpful to identify those who are most likely to benefit," says Andrew T. Chan, MD, MPH, of the MGH Gastrointestinal Unit, the paper's lead author. "We decided to look at the gene for an enzyme that metabolizes aspirin and is known to have variant forms that slow down that process."
The Nurses' Health Study has followed more than 120,000 female registered nurses since the mid-1970s, asking them to complete a questionnaire on risk factors for cancer and cardiovascular disease every two years. In 1980, assessments of diet, aspirin use, and colon examination were added to the NHS questionnaire, and in 1990 many participants provided blood samples that could be analyzed for genetic factors.
The current study analyzed the blood samples from participants who reported having endoscopic colon examinations between 1990 and 1998. About 500 of those participants had been diagnosed with adenoma - a type of colorectal polyp that may develop into cancer - and their data was compared with a control group consisting of an equal number of women not diagnosed with polyps.
While the incidence of polyps was significantly lower in those who took aspirin regularly - defined as two or more tablets per week - that benefit was primarily seen in participants with variant forms of the enzyme known as UGT1A6. Among participants with the most common form of the enzyme, the improvement in risk was not statistically significant. As in previous studies, the higher the intake of aspirin, the greater the risk reduction, but again that improvement was strongest in those with the altered form of the enzyme.
"These altered genes slow the metabolism of aspirin so it may linger in the body longer. This could explain why aspirin may have a stronger effect in preventing polyps for these slow-metabolizers," says Chan. "But the persistence of aspirin in the body could also increase the risk for side effects like bleeding. Until we can get a more complete picture of the risks and benefits, which will require larger studies, we can't make any definitive recommendations about preventive aspirin therapy." Chan is an instructor in Medicine at Harvard Medical School.
The Nurses' Health Study (NHS) was initiated in 1976 at BWH and is the longest-running, major women's health study ever undertaken. The NHS 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.
Coauthors of the JNCI study are Charles Fuchs, MD, MPH, senior author, of DFCI and BWH; Edward Giovannucci, MD, ScD, and David Hunter, MD, ScD, of BWH and the Channing Laboratory at Harvard Medical School; and Gregory Tranah, PhD, of the Harvard School of Public Health. The research was supported by grants from the American Gastroenterological Association, the National Institutes of Health and the National Colorectal Cancer Research Alliance.
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.
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