Aspirin's potential ability to prevent
colon polyps may not apply equally to all
Benefit may be confined primarily
to those with certain genetic variants, more research needed
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
"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.
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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