Study reveals aspirin's colorectal
cancer prevention mechanism
Prevention restricted to tumors expressing
COX-2, may help identify those most likely to benefit
BOSTON - May 23, 2007 - Aspirin therapy's ability to reduce
the risk of colorectal cancer, an association seen in a large number
of studies, appears to depend on the drug's inhibition of the COX-2
enzyme, the action that also underlies aspirin's usefulness for
treating pain and inflammation. In the May 24 New England Journal
of Medicine, investigators from Massachusetts General Hospital
Cancer Institute and Brigham and Women's Hospital report that
regular aspirin intake only reduced the incidence of colorectal
tumors that overexpress COX-2.
"We knew that aspirin can block COX-2 function and that COX-2
is present in the vast majority of colorectal tumors but not in
normal colon tissue," explains Andrew Chan, MD, MPH, of the
Gastrointestinal Unit, the paper's lead author. "Therefore
we hypothesized that, if blocking the COX-2 pathway was the mechanism
underlying aspirin-associated risk reduction, it should preferentially
reduce the incidence of those tumors that rely on COX-2."
To investigate that theory, the research team compiled data from
two ongoing prospective research studies - the Nurses
Health Study (NHS) and the Health
Professionals Follow-up Study (HPFS). Both studies gather comprehensive
health information on their participants every two years, data which
is analyzed for associations between factors such as diet and the
incidence of several diseases. Both the NHS, which enrolls more
than 120,000 female registered nurses, and the HPFS, following more
than 50,000 men employed in the health professions, have previously
found associations between aspirin intake and reduced colorectal
For the current study, the researchers focused on almost 83,000
NHS participants and about 47,000 HPFS participants for whom necessary
information was available. They received permission to acquire medical
records and pathology reports from those who had reported being
diagnosed with colorectal cancer, then retrieved more than 600 pathology
specimens from participants whose diagnoses could be confirmed.
The samples were analyzed for expression of COX-2.
As seen in previous reports, among the more than 120,000 participants,
those who took at least two standard aspirin tablets a week had
about three-quarters the risk of colorectal cancer that aspirin
non-users did. However, analysis of tumor samples showed that reduction
in risk only applied to tumors that expressed COX-2. The incidence
of COX-2-negative tumors was virtually the same among those who
did and did not take aspirin.
"These results will allow us to test another hypothesis: that
in patients who have had colorectal cancer or polyps in the past,
expression of COX-2 in the earlier lesion might indicate those for
whom aspirin could reduce the risk of recurrence," says Charles
Fuchs, MD, MPH, of Dana-Farber, the study's senior author. "Answering
that will be our next target."
Both researchers note that current evidence does not support generally
recommending aspirin therapy to reduce colorectal cancer risk. "For
most people, the best way to prevent colorectal cancer is through
screening, which we know saves lives by allowing us to treat polyps
before they become cancers," says Chan.
Fuchs adds, "An individual who has had colorectal cancer in
the past is at higher risk for subsequent tumors, and that might
be someone who should discuss the advisability of taking aspirin
with his or her primary care physician. We hope that our future
research will further clarify who would benefit most from regular
aspirin therapy and that understanding the mechanism of this effect
will lead to new preventive and treatment strategies."
Fuchs is an associate professor of Medicine at Harvard Medical School,
where Chan is an assistant professor of Medicine. Study co-author
Shuji Ogino, MD, PhD, is an HMS assistant professor of Pathology
at Brigham and Women's Hospital. The study was supported by grants
from the National Cancer Institute, the National Institutes of Health,
the Bennett Family Fund for Targeted Therapies Research, the Entertainment
Industry Foundation National Colorectal Cancer Research Alliance,
the Marshall S. Kates Memorial Fund, and the Foundation for Digestive
Health and Nutrition.
Massachusetts General Hospital 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 major
research centers in AIDS, cardiovascular research, cancer, computational
and integrative biology, cutaneous biology, human genetics, medical
imaging, neurodegenerative disorders, regenerative medicine, systems
biology and physiologic genomics, transplantation biology, and photomedicine.
Dana-Farber Cancer Institute is a principal teaching affiliate
of the Harvard Medical School and is among the leading cancer research
and care centers in the United States. It is a founding member of
the Dana-Farber/Harvard Cancer Center (DF/HCC), a designated comprehensive
cancer center by the National Cancer Institute.
Media Contact: Sue
McGreevey, MGH Public Affairs
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