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Researchers find biological links between red meat and colorectal cancer
WASHINGTON, June 19, 2021 (BSS/AFP) – 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.
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.
BSS/AFP/GMR/1131 hrs