Better Screening		Medical Genetics
Questions & Answers		Research Update

Better Screening and Treatment
are Goals of National Registry
A major effort to develop a national colorectal cancer registry is under way at the Cleveland Clinic. We are one of only six U.S. medical centers chosen to work collectively to develop this registry, supported by the National Cancer Institute. The creation of a national registry will help us better understand the causes of hereditary colorectal cancer and may lead to better screening techniques and medical therapies. We hope to identify more than 1,200 families with two cases of colorectal cancer and about 400 families with at least three cases of colorectal cancer. For more information about the national registry, call our Medical Genetics Program at 216/445-5686.

During the past year, we have experienced important changes in our registries and some significant advances in the field of inherited colorectal cancer. A major breakthrough in research was the identification of a genetic mutation – found only among the Ashkenazi Jewish population – that causes familial colorectal cancer, along with a simple blood test that can identify it. (See “Question & Answer” article on page 3.)

Important Syndromes within our Registries
The Cleveland Clinic’s Jagelman Registries are among the largest in the world. Our physicians are internationally recognized for their expertise and are often called upon to help other institutions establish their own registries. The information learned from our patients and registries gives us the opportunity to better understand, treat and research inherited colorectal cancer and forms the cornerstone of our quality assessment efforts.

Below, we define three major syndromes of inherited colorectal cancer.

Familial Adenomatous Polyposis (FAP) is a dominantly inherited condition in which each child has a 50 percent risk of inheriting the disease. FAP makes up about 1 percent of the 130,000 colorectal cancers diagnosed each year. A mutation in the APC gene causes a generalized disorder of cell growth that leads to tumors in several organs, particularly the large intestine. Here, hundreds or thousands of adenomatous polyps grow. One or more of these adenomas will become cancerous unless they are removed. Diagnosis is made by sigmoidoscopy or by genetic testing, usually started in puberty. Skin cysts, bony lumps or extra teeth are also signs of FAP. Once a diagnosis is made, the colon needs to be removed. This can be done safely with minimal impact on lifestyle. For severe cases the colon and rectum need to be removed. Fortunately, Clinic colorectal surgeons can perform a pouch procedure that avoids the need for a permanent ileostomy (bag). During the past year, we have added 20 new families to the FAP registry. These new patients and their families give us the opportunity to better understand and treat the disease.

Hereditary Nonpolyposis Colorectal Cancer (HNPCC) is caused by mutations in genes that normally repair damage to the DNA in our cells. HNPCC accounts for 5 percent of the 130,000 colorectal cancers diagnosed each year. It’s similar to FAP in that it is dominantly inherited, but different in that it doesn’t produce excessive numbers of polyps in the colon. HNPCC is suspected in families where colon cancer occurs in young patients, typically under the age of 50; and where three or more cases occur in close relatives. Cancers of the uterus, ovary, urinary tract, stomach and small intestine also can be found in these families. Diagnosis of HNPCC is made by the strength of the family history or by genetic testing. Surgery is not routine unless a large polyp or cancer is already present. Preventive efforts are directed to frequent screening tests that include colonoscopy, pelvic examinations and urine cytology. These begin early, when patients are in their twenties or thirties.

Familial Colorectal Cancer (FCC) Patients without polyposis whose family history of colon and rectal cancer is not strong enough to fit HNPCC are grouped here. FCC accounts for anywhere from 10 to 50 percent of the 130,000 new colorectal cancers reported each year. A new genetic test can help determine the risk of FCC by identifying the presence of a genetic mutation. This mutation appears to occur only in those of Ashkenazi (Eastern and Central European) Jewish descent. For those whose risk cannot be determined by genetic testing, screening with colonoscopy should begin about 10 years before the age at which the youngest relative with colorectal cancer was diagnosed.

There are 396 FAP families (almost 4,000 patients), 90 HNPCC families (1,000 patients) and 240 FCC families (2,000 patients) in the Jagelman registries. Also included are two rarer syndromes that cause colorectal cancer: juvenile polyposis and Peutz-Jehger’s polyposis. For more information about these syndromes, please call the Inherited Colorectal Cancer Registries at 216/444-6470 or 800/998-4785.