Genetic testing for Colon Ca

OB/GYN News, Nov 15, 2001 by Sally Koch Kubetin

Commercially available genetic testing is now the screening method of choice for hereditary colorectal cancer, Dr. Francis M. Giardiello said at the annual meeting of the American Society of Colon and Rectal Surgeons.

Before these tests were available, atrisk family members had to undergo frequent endoscopic evaluations for decades. Now, individuals who have negative results on genetic testing can be safely spared frequent procedures, said Dr. Giardiello of the Johns Hopkins University; Baltimore.

Most people at risk for familial colorectal cancer don't have one of the few well defined disorders for which genetic testing is available, Dr. Giardiello noted. Close to 20% of all cases of colorectal cancer cluster in families, and the disorders for which genetic tests are available account for only about 3% of all colorectal cancer in the United States. Genetic testing is commercially available for:

* Familial adenomatous polyposis (FAP). The screening test of choice is an adenomatous polyposis coli (APC) gene test, which should be done at age 10-12 years, following formal pretest genetic counseling and informed consent of both patient and parents. If the APC gene test is positive in an at-risk child, yearly sigmoidoscopy is recommended.

* Attenuated FAR Patients with classic FAP can be followed via sigmoidoscopy; those with attenuated FAP require colonoscopy because their polyps cluster on the right side of the colon, out of the reach of flexible sigmoidoscopy.

* I1307K mutation of the APC gene. Dr. Giardiello was one of the discoverers of this mutations, which is found only among Ashkenazi Jews.

The prevalence of the 11307K mutation among the American Ashkenazi Jewish population is 6%. "The lifetime risk of colon cancer in the Ashkenazi Jewish population is about 10%. If a patient has a positive test for an 11307K mutation, risk increases to 20%. So consider genetic counseling and genetic testing in Ashkenazi Jews with a family history of colorectal cancer," Dr. Giardiello advised.

* Hereditary nonpolyposis colon cancer. Genetic testing can be done by screening for mutations in the MSH2 or MLH1 mismatch repair gene or by searching a patient's tumor for microsatellite instability.