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Health & Medicine for Senior Citizens
New Insights Into How Cancer Develops May Lead to New Early Screening Opportunity
A new appreciation of the genetic changes that occur
as precancerous cells turn malignant could help
researchers design new early detection screening
Dec. 4, 2013 –
Hutchinson Cancer Research Center
studying the precancerous condition
Barrett’s esophagus have shown that rather
than resulting from a steady accumulation of
small genetic mutations, cancer arises a few
years after cells begin to undergo large,
drastic mutations. This insight could help
researchers detect cells on the cusp of
becoming malignant and distinguish benign
from dangerous pre-cancerous conditions.
This new evidence of
how cancer cells evolve could help
scientists design better screening methods
to catch cancer before it advances.
“Cancer’s a frightening
word,” said Brian Reid, M.D., a cancer
geneticist at Fred Hutch who led the study.
But the results should
reassure patients, Reid said, because
researchers are gaining a better
understanding of how to increase the window
of opportunity to detect potentially
dangerous cancers before they’re hard to
treat. The findings are published
Cancer Prevention Research.
Most tumors are benign
and slow-growing, posing little risk to
patients. According to the standard cancer
model, cells acquire mutations at a
relatively steady rate, and a faster rate
results in a faster-developing and more
dangerous cancer. But this model couldn’t
explain why regular screening reliably
detects benign tumors while often missing
Reid’s work helps
explain this phenomenon. He studies
Barrett’s esophagus (BE), a precancerous
condition caused by chronic heartburn. Only
about 5 percent of BE patients progress to
cancer, but often their tumors are not
identified early enough for successful
treatment, even with regular screenings.
To understand the
genome changes distinguishing BE cells that
progress to cancer from those that don’t,
Reid and his team examined esophageal tissue
samples taken from BE patients at regular
intervals. They found that despite the
highly mutagenic nature of acid reflux, the
cells from non-progressing patients acquired
almost no mutations ― even after years of
exposure to stomach acid.
But in patients who
ultimately progressed to esophageal cancer,
Reid and his colleagues saw a sudden change
about four years prior to cancer diagnosis.
These cells seemed to tip suddenly toward a
cancerous path, undergoing large,
catastrophic mutations such as deletions of
long stretches of chromosomes or doubling of
This was contrary to
what Reid expected to find. “We thought we’d
find a fast rate of mutation [in progressors]
and a slow rate [in non-progressors],” he
said, noting that the striking findings are
in keeping with recent observations by other
researchers. Other studies examining
ovarian, prostate, breast, and colon cancer
have observed a pattern of drastic mutations
and genome doubling.
Because the findings
seem to be generalizable to other types of
cancers, Reid is optimistic that they are a
first step toward better screening and
The four-year window in
which BE cells take a turn for the malignant
should reassure patients, Reid said. It
gives physicians plenty of time to identify
cancerous cells, and findings like Reid’s
and others’ are giving researchers a better
picture of how to detect premalignant cells
as they begin to progress toward cancer.
It may be that
researchers will identify even earlier,
smaller mutations that presage these cells’
malignant future, extending the window of
opportunity by several years. Additionally,
research into less invasive screening tests
may well make invasive screening methods
like endoscopies a thing of the past.
Ideally, Reid noted,
researchers will discover ways to stop
precancerous cells before the tipping point.
Such interventions may
be as simple as popping a few aspirin, as
research by Reid and his colleagues has
already demonstrated that high-risk BE
patients who use aspirin and non-steroidal
anti-inflammatories cut their esophageal
cancer risk by about half.
“If something like that
could be implemented, it would be a huge
victory for patients,” Reid said.
The good news, he said,
is that “most Barrett’s esophagus patients
won’t get cancer in their lifetime”― and
less invasive tools to increase the window
of detection are on the horizon.
Cancer Research Center, home to three Nobel
laureates, interdisciplinary teams of world-renowned
scientists seek new and innovative ways to prevent,
diagnose and treat cancer, HIV/AIDS and other
life-threatening diseases. An independent, nonprofit
research institute based in Seattle, Fred Hutch
houses the nation’s first and largest cancer
prevention research program, as well as the clinical
coordinating center of the Women’s Health Initiative
and the international headquarters of the HIV
Vaccine Trials Network.
Private contributions are essential for enabling
Fred Hutch scientists to explore novel research
opportunities that lead to important medical
breakthroughs. For more information visit
www.fredhutch.org or follow Fred Hutch on