Nearly 160 Canadians die every week from colorectal cancer.
The numbers are staggering and current screening methods
are obviously not detecting the disease early enough but
a recent study may have uncovered the root of the problem.
Serrated polyps, a type of colonic polyp that has up till
now been considered completely benign, has been implicated
in a newly discovered type of inherited colon cancer,
according to research published in the March issue of
Clinical Gastroenterology and Hepatology.
Currently, two major forms of hereditary
colorectal cancers have been identified — familial
adenomatous polyposis (FAP) and hereditary nonpolyposis
colon cancer (HNPCC). However, these types only account
for about 2-5% of all colorectal cancers, while family
histories suggest that 5-15% of colorectal cancers have
a genetic cause. The new study suggests that monitoring
patients with serrated polyps might help us pick up
on more of these mystery cases.
"It's increasingly apparent that
bowel cancer is really an umbrella term for a collection
of quite different diseases," says study author Dr Jeremy
Jass who holds a Canada Research Chair in Gastrointestinal
Pathology at Montreal's McGill University. Now it appears
another form may be added to the list.
"It's well-known that I'm interested
in early-onset disease, so I receive samples from around
the world," says Dr Jass. "It's clear that there's a
subset with variable MSI, high DNA methylation and BRAF
mutation that don't fit existing models." Microsatellite
instability (MSI) is a measure of the frequency of small
insertions and deletions in tracts of repetitive DNA.
HNPCC cancers are generally characterized by a high
degree of MSI, which is usually a sign of a good prognosis.
But the newly observed class of inherited cancers shows
major variation in MSI status within families, possibly
suggesting a worse average prognosis.
In his latest research, Dr Jass
and colleagues from Australia and Japan examined the
biopsy records of 287 Australian families from Queensland
with multiple cases of colorectal cancer. Nearly half
were identified as HNPCC, with all affected family members
having high MSI. But 45 families showed variable MSI,
DNA methylation and BRAF activity — the criteria
for the new form of hereditary colon cancer.
The age of onset for this new form
of colon cancer is generally younger than that seen
in HNPCC, which is already lower than the typical age
of onset of sporadic colorectal cancer. The condition
appears to be more common in women, and the tumours
generally arise on the less accessible right side of
the colon, home to the majority of serrated polyps.
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It isn't clear what proportion of such cancers might
be inherited, and how many sporadic cancers have a similar
pathway. "We don't even know how rare HNPCC is yet,
and we've known about that for 10 years," says Dr Jass.
What is apparent is that serrated
polyp can no longer be ignored, even in people without
a family history of colorectal cancer. "The real question,"
concludes Dr Jass, "is what sort of followup is necessary
in patients with these serrated polyps. I think it's
becoming clear that we'll need to revise our guidelines
on that."
Clin Gastroenterol Hepatol
Mar 2005;3(3):254-63
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