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 screening—annual FOBT and sigmoidoscopy every three to five years—for 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.
