WASHINGTON“A positive family history is the most common risk factor
for large bowel malignancy other than age,” Randall W. Burt, MD, of the
University of Utah Health Sciences Center, said at a symposium on colorectal
cancer at Digestive Disease Week, sponsored by the American Gastroenterological
Association and the American Society for Gastrointestinal Endoscopy.
The risk with a positive family history (see table)
varies from a modestly elevated risk when an older relative is affected
with colon cancer or an adenomatous polyp, to a significantly higher risk
associated with increased numbers of first-degree relatives any of whom
are diagnosed at a relatively young age, he said.
While testing is available to determine a genetic predisposition to
colon cancer, Dr. Burt advised caution in its use. Genetic testing does
not work well, he warned, “if you are just exploring. It can only be used
in the setting of known syndromes of colon cancer.”
To test with certainty for mutations of the FAP (familial adenomatous
polyposis) gene, it is necessary to first test a family member known to
have the disease. Other family members can then be tested with close to
100% reliability. Those testing positive should have sig-moidoscopy screening
every one to two years beginning at age 10 to 12, he said.
The 3-2-1 Rule for HNPCC
To identify families that have hereditary nonpolyposis colorectal cancer
(HNPCC), also called the Lynch syndrome, Dr. Burt recommends application
of the “Three-Two-One Rule” (the Amsterdam criteria): The presence of three
first-degree relatives with colon cancer in two successive generations,
one of whom having been diagnosed at less than 50 years of age.
If the family meets the three-two-one criteria, the genetic mutation will
be found in 50% to 70% of family members upon genetic testing.
Again, to test for the mutation it is necessary to first test a family
member known to have colon cancer, preferably a first-degree relative diagnosed
when younger than age 50. The mutations found in that individual will indicate
the mutation for the rest of the family.
Up to 96% of colon cancer cases occur outside the inherited syndromes.
Nevertheless, familial clustering of cases is not unusual. Colon cancer
can indeed “run in families,” and the presence of affected relatives does
increase the risk of malignancy. The lifetime risk of this disease in the
general population in the United States is about 6%, so chance clusters
of cases are frequently observed.
Controlled genetic epidemiology studies have consistently demonstrated
a two- to threefold increased risk of colon cancer in the first-degree
relatives of persons with this malignancy. The increase is significantly
less when a second- or third-degree relative is involved.
In view of these risks, Dr. Burt advised standard screeningannual FOBT
and sigmoidoscopy every three to five yearsfor all relatives of those
with colon cancer or polyps, beginning at age 35 to 40. Further, if two
or more first-degree relatives have colon cancer, or if a first-degree
relative is diagnosed at age 50 or less, colonoscopy should be considered.