WASHINGTON, United States — Eating less red meat is
standard medical advice for preventing colorectal cancer, but the way it causes
cells to mutate has remained unclear, and not all experts were convinced there
was a strong link.
اضافة اعلان
A new paper in the journal Cancer Discovery has now identified
specific patterns of DNA damage triggered by diets rich in red
meat — further
implicating the food as a carcinogen while heralding the possibility of
detecting the cancer early and designing new treatments.
Prior research establishing the connection was mainly
epidemiologic, meaning that people who developed the condition were surveyed on
their eating habits, and researchers spotted associations with colorectal
cancer incidence.
But a lack of clarity around the biology meant that the case
wasn't quite slam dunk, and in 2019, one team of researchers made waves when
they declared they only had a "low" degree of certainty that reducing
consumption would prevent cancer deaths.
"When we say red meat is carcinogenic, and that it
impacts incidence of cancer, there has to be some plausible way by which it
does it," Dana-Farber Cancer Institute oncologist Marios Giannakis, who
led the new study, told AFP.
After all, scientists discovered long ago which chemicals in
cigarette smoke are to blame for cancer, and how certain bands of UV light
penetrate the skin and trigger mutations in genes that control how cells grow
and divide.
To address the knowledge gap, Giannakis and his colleagues
sequenced DNA data from 900 patients with colorectal cancer, who were drawn
from a much larger group of 280,000 health workers participating in a
years-long studies that included lifestyle surveys.
Detective work
The strength of this approach is that the people documenting
their diet had no way of knowing of their future
cancer diagnosis, rather than
asking people to recall their eating habits after they became ill.
The analysis revealed a distinct mutational signature — a
pattern that had never before been identified but was indicative of a type of
DNA damage called "alkylation."
Not all cells that contain these mutations will necessarily
become cancerous, and the signature was present in some healthy colon samples
too.
The mutation signature was significantly associated with
intake of red meat, both processed and unprocessed, prior to the patient's
diagnosis of cancer, but not with the intake of poultry, fish or other
lifetsyle factors that were examined.
"With red meat, there are chemicals that can cause
alkylation," explained Giannakis.
The specific compounds are nitroso compounds that can be
made from heme, which is plentiful in red meat, as well as nitrates, often
found in processed meat.
The mutation patterns were strongly associated with the
distal colon -- the lower part of the bowels that leads to the anal canal,
which is where past research suggested colon cancer linked to red meat mostly
occurs.
What's more, among the genes that were most affected by the
alkylation patterns were those that previous research has shown are among the
most common drivers of colorectal cancer when they mutate.
Taken as a whole, the multiple lines of evidence build up a
compelling argument, said Giannakis, likening the research to careful detective
work.
Moderation urged
In this case, the suspicious mutation signature has a lot to
answer for: patients whose tumors had the highest levels of alkylation damage
had a 47 percent greater risk of colorectal cancer-specific death, compared to
patients with lower levels of damage.
But Giannakis, also a practicing doctor, said it was
important to focus on how the research can be used to help patients.
Future work might help physicians identify which patients
are genetically predisposed to accumulating alkylation damage, then counsel
them to limit their red meat intake.
Identifying patients who have already started to accrue the
mutational signature could help identify who's at greater risk of developing
cancer, or catch the disease at an earlier stage.
And because the amount of alkylation damage appears to be a
biomarker of patient survival, it could possibly be used to tell patients about
their prognosis.
Finally, understanding the biological pathway through which
colorectal cancer occurs paves the way for medicines that interrupt or reverse
the process, preventing the disease.
Giannakis stressed the takeaway message is not that people
should totally abstain from red meat: "My recommendation would be
that moderation and a balanced diet is key."
High levels of tumor alkylation damage were only seen among
patients eating on average more than 150 grams (five ounces) a day, roughly
equal to two or more servings.
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