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 Two decades after scientists discovered that aspirin
might reduce the risk of colorectal cancer, a new study finds that
it has that benefit almost exclusively in people with genes that
produce high levels of a particular enzyme. Those whose DNA produces
low levels of the enzyme benefit hardly at all, scientists reported
on Wednesday in the journal Science Translational Medicine.
"If you have low levels of (the enzyme), taking aspirin to reduce
your colon cancer risk is probably not helping you," said Dr.
Sanford Markowitz, professor of cancer genetics at Case Western
Reserve School of Medicine in Cleveland and co-leader of the study.
"But people with higher levels are getting a bang for the buck: The
combination of high enzyme levels plus taking aspirin really seems
to be the key to measurably reducing colon cancer risk."
Identifying who can cut their risk of colorectal cancer, which the
American Cancer Society projects will kill 50,000 people in the
United States this year, by taking aspirin is especially important
because the drug poses a significant risk of ulcers and
gastrointestinal bleeding, which can be fatal.
Because the gastrointestinal dangers are too great to justify the
uncertain benefits, the U.S. Preventive Services Task Force, which
advises the government, recommends against the use of aspirin to
prevent colorectal cancer in the general population.
"But if you could tailor prevention to people who have both a high
risk of the disease and the greatest likelihood of benefiting from
it, that could change the balance," said Dr Andrew Chan of
Massachusetts General Hospital in Boston, who co-led the study.
TARGETING PROSTAGLANDINS
Both the enzyme, called 15-PGDH, and aspirin target prostaglandins.
These molecules promote the growth of colon cells and also
inflammation; both increase the risk of cancer.
Aspirin inhibits production of prostaglandins. The enzyme chews them
up. Result: lower levels of cancer-promoting molecules.
Chan and his team mined the long-running Nurses' Health Study and
the Health Professionals Follow-Up Study, both based at Harvard
School of Public Health and sister institutions. Among the 127,865
participants were 270 cases of colorectal cancer for which the
Boston team had records of aspirin use.
Markowitz's team them determined the levels of the genetic material
that produces 15-PGDH in the patients' colons.
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In people whose DNA produces high levels of the enzyme, regular
aspirin use reduced the risk of colorectal cancer by half, and
possibly by as much as two-thirds. In people with lower levels,
aspirin use reduced risk by only 10 percent, and may have increased
it. "That represents a clean yes-or-no about who would benefit from
aspirin," Markowitz said. In any research that examines what people do on their own rather
than what they're assigned to do as part of a study - in this case,
take aspirin or not - it's always possible that something other than
the factor scientists focused on caused the different health
effects. Chan and his team are confident they eliminated smoking,
eating meat, drinking alcohol and other lifestyle factors as
explanations for the different colon-cancer rates, leaving only
aspirin and enzyme levels.
"But there is always a chance that something else is going on and we
don't know it, like all the high-PGDH people were also marathon
runners" or had some other trait that slashed their cancer risk,
said Markowitz, who is also a medical oncologist at University
Hospitals Case Medical Center.
About half the U.S. population produces high levels of the enzyme
in the colon, and half produce low levels. Neither blood nor genetic
testing is reliable for the enzyme, Markowitz said, but its levels
can be measured via colon biopsy, which can be done during a routine
colonoscopy.
The people most likely to benefit from aspirin, in terms of
colorectal cancer, are those with a family history of the disease or
a personal history of certain polyps, and should have screening
colonoscopies anyway, Markowitz pointed out.
An earlier study, in lab mice, found that 15-PGDH seemed to boost
the ability of celecoxib (sold by Pfizer as Celebrex) to prevent
colon tumors. But with low 15-PGDH levels, the drug had no such
benefit. It is likely, Markowitz said, that in people, too,
celecoxib's effect on the risk of colon cancer depends on 15-PGDH
levels.
(Reporting by Sharon Begley; editing by Jonathan Oatis)
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