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.
WASHINGTON“A positive family history is the most common risk factorfor large bowel malignancy other than age,” Randall W. Burt, MD, of theUniversity of Utah Health Sciences Center, said at a symposium on colorectalcancer at Digestive Disease Week, sponsored by the American GastroenterologicalAssociation 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 affectedwith colon cancer or an adenomatous polyp, to a significantly higher riskassociated with increased numbers of first-degree relatives any of whomare diagnosed at a relatively young age, he said.
While testing is available to determine a genetic predisposition tocolon cancer, Dr. Burt advised caution in its use. Genetic testing doesnot work well, he warned, “if you are just exploring. It can only be usedin the setting of known syndromes of colon cancer.”
To test with certainty for mutations of the FAP (familial adenomatouspolyposis) gene, it is necessary to first test a family member known tohave the disease. Other family members can then be tested with close to100% reliability. Those testing positive should have sig-moidoscopy screeningevery 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 applicationof the “Three-Two-One Rule” (the Amsterdam criteria): The presence of threefirst-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 willbe found in 50% to 70% of family members upon genetic testing.
Again, to test for the mutation it is necessary to first test a familymember known to have colon cancer, preferably a first-degree relative diagnosedwhen younger than age 50. The mutations found in that individual will indicatethe 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 cancercan indeed “run in families,” and the presence of affected relatives doesincrease the risk of malignancy. The lifetime risk of this disease in thegeneral population in the United States is about 6%, so chance clustersof cases are frequently observed.
Controlled genetic epidemiology studies have consistently demonstrateda two- to threefold increased risk of colon cancer in the first-degreerelatives of persons with this malignancy. The increase is significantlyless when a second- or third-degree relative is involved.
In view of these risks, Dr. Burt advised standard screeningannual FOBTand sigmoidoscopy every three to five yearsfor all relatives of thosewith colon cancer or polyps, beginning at age 35 to 40. Further, if twoor more first-degree relatives have colon cancer, or if a first-degreerelative is diagnosed at age 50 or less, colonoscopy should be considered.
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