Identifying and Managing Risk for Hereditary Colorectal Cancer: Screening and Genetic Testing.

Colorectal Cancer is the second leading cause of cancer death in the United States. It is estimated that, of the 150,000 cases of colorectal cancer diagnosed each year 5% are inherited. This number may rise as more patients are identified by genetic testing for hereditary colorectal cancers. Awareness of both patients and their heath care workers of hereditary colorectal cancer are vital. Identifying individuals with hereditary colorectal cancers is important for the prevention, surveillance and treatment of both patients and their families.

What are my risks of developing hereditary colorectal cancer?
In the general population the lifetime risk of developing colorectal cancer is 2%, this number increases to 8% with individual with one first-degree relative with colorectal cancer and 17% when 2 first-degree relatives are affected.

How do we identify individuals with hereditary colorectal cancer?
The three most commonly identified hereditary colorectal cancer syndromes are: Familial Adenomatous Polyposis (FAP), Attenuated Familial Adenomatous Polyposis (AFAP) and Hereditary Nonpolyposis Colorectal Cancer (HNPCC). These syndromes are inherited in an autosomal dominant fashion (i.e., each first-degree relative of a carrier has a 50% chance of having inherited the cancer associated mutation).

FAP and AFAP
FAP is characterized by multiple adenomatous colon polyps, which in some cases may be more than 100. At age 15, 50% of FAP patients develop polyps and 95% develop polyps at age 35. Left untreated 100% of FAP patients develop colorectal cancer with the average age of developing cancer is 34 to 43 years of age. AFAP is a less sever form of FAP characterized by fewer polyps (> 20) and later onset of colorectal cancer. Fortunately, FAP is rare and accounts for less than 1% of colorectal cancers.

HNPCC
HNPCC is much more common and accounts for about 5% of colorectal cancers. HNPCC is characterized by colorectal cancers diagnosed at an early age, usually before age 50. Cancers are more common on the right side of the colon. Polyps are few as compared to multiple polyps in FAP. Family history of an individual with HNPCC may show the following characteristics:

1. First-degree relative with colorectal cancer diagnosed before 50.
2. At least 2 generations of colorectal cancers in patient family.
3. Personal history of colon polyp and first degree relative with adenomas (polyps) diagnosed before age 40.
4. Two or more relatives with colorectal cancer with HNPCC associated cancers (e.g. cancers of the uterus, ovary, kidney/ureter, stomach and small bowel) one of who is a first-degree relative.

Studies have shown that individuals with HNPCC have up to an 85% chance of developing colorectal cancer during their lifetime.

Genetic testing identifies individuals at risk.
To identify individuals with HNPCC, FAP and AFAP a thorough cancer family history is essential. Individuals who fulfill specific clinical criteria should be evaluated by their heath care provider for further genetic counseling and possible testing. The following are guidelines used to identify individuals at risk.

Hereditary Nonpolyposis Colorectal cancer (HNPCC)
»	Patient with colorectal cancer (CRC) and a first-degree relative with:
	* CRC or HNPCC related cancer (endometrial, ovarian, stomach, kidney, brain, and or small bowel cancers) one diagnosed before the age of 50.   OR  * Colorectal adenoma (polyp) before age 40.
»	Patient diagnosed with 2 HNPCC related cancers (endometrial, ovarian, etc.)
»	Relatives of patients with a positive genetic test for HNPCC (confirmed MLH1 or MSH2 mutation)

Familial Adenomatous polyposis (FAP) and attenuated FAP (AFAP)
»	Patients affected with FAP (> 100 colorectal polyps)
»	Patient with suspected AFAP (> 20 cumulative colorectal polyps)
»	1st-degree relatives of patients with FAP or AFAP
»	Relatives of patient with positive genetic test for FAP or AFAP (APC mutation)

How Can I Be Tested?
Individuals with any of the above risk factors are provided with pretest genetic counseling. During counseling patients, fears and concerns about test results are addressed. Issues such as sharing tests results with family members, long term implications of a positive test results such as cancer screening and treatment, and health insurance considerations are discussed. After appropriate pretest counseling and informed consent, testing is done by obtaining a blood sample. Testing is done at a genetic testing laboratory. If you have any questions about getting testing, or whether you or your family are a candidate for testing please contact us at 937.435.8663. We provide a comprehensive program, which involve patient screening, follow-up evaluation and surgical treatment if needed.