Familial adenomatous polyposis (FAP)

Familial adenomatous polyposis, or FAP is a hereditary colon cancer syndrome in which the affected family members develop large numbers (hundreds, sometimes thousands) of colon polyps starting in their teens. Unless the condition is detected and treated early (treatment involves removal of the colon), a family member with the FAP syndrome is almost sure to develop colon cancer. Cancers most commonly begin to appear when patients are in their 40's, but can appear earlier. These patients also are at risk of developing other cancers such as cancers of the thyroid gland, stomach, and the ampulla (the part of the duodenum into which the bile ducts drain).

Attenuated familial adenomatous polyposis (AFAP)

Attenuated familial adenomatous polyposis, or AFAP is a milder version of FAP. Affected patients develop less than 100 colon polyps. Nevertheless, they are at high risk of developing colon cancers at a young age. They are also at risk for stomach and duodenal polyps.

Hereditary nonpolyposis colon cancer (HNPCC)

Hereditary nonpolyposis colon cancer, or HNPCC, is a hereditary cancer syndrome in which affected family members tend to develop colon cancers, usually in the right colon, in their 30's to 40's. Certain HNPCC patients also are at elevated risk for developing uterine cancer, stomach cancer, ovarian cancer, cancers of the ureters (the tubes that connect the kidneys to the bladder), cancers of the bile ducts (the ducts that drain bile from the liver to the intestines), and cancer of the brain and skin.

MYH polyposis syndrome

The MYH polyposis syndrome is a recently discovered hereditary colon cancer syndrome. Affected patients typically develop 10-100 polyps during their 40's and are at high risk for developing colon cancer. The MYH syndrome is inherited in an autosomal recessive manner with each parent contributing one copy of the mutant gene. Most people with the MYH syndrome do not have a multigenerational family history of polyps or cancer of the colon but may have brothers or sisters with it.

Who should consider genetic counseling and testing?

Genetic counseling followed by genetic testing should be considered for individuals as well as their family members when there are:

• Individuals in the family with early onset of colon cancer, before age 50
• Individuals in the family with numerous colon polyps
• Families in which multiple members have colon cancer
• Families with members with numerous colon polyps
• Families with members having colon cancers at young ages
• Families with members having certain non-colon cancers such as cancers of the uterus, thyroid, ureters, ovaries, small intestine, etc.

Genetic testing without prior counseling is discouraged because of the extensive family education that is involved and the complicated nature of interpreting the test results.

Why is genetic counseling and testing important in hereditary colon cancer syndromes?

Patients who have hereditary colon cancer syndromes usually have no symptoms and are unaware that they have colon polyps or early colon cancers. They usually will develop colon cancers early in life (often before ages 40-50). Therefore, to prevent colon cancers in patients with hereditary colon cancer syndromes, colon screening must begin early. For example, patients with FAP should have annual flexible sigmoidoscopies starting at age 12, patients with AFAP should have annual colonoscopies starting at age 25, and patients with HNPCC should have colonoscopies beginning at age 25 (or 10 years younger than the earliest colon cancer diagnosed in the family, whichever is earlier). The current screening recommendations for the general population (fecal occult blood testing, flexible sigmoidoscopy, and colonoscopy beginning at ages 40-50) are inadequate for most patients with hereditary colon cancer syndromes.

Genetic counseling and testing are important to identify patients and family members with hereditary colon cancer syndromes so that screening with flexible sigmoidoscopies and colonoscopies can begin early and, if necessary, the colon can be removed surgically to prevent colon cancer. Moreover, depending on which hereditary colon cancer syndrome is present, early screening for other types of cancer such as ovarian, uterine, stomach, ureter, and thyroid may be appropriate.

How is genetic testing conducted?

Genetic testing should be done following genetic counseling, so that family members understand fully the advantages and limitations of genetic testing as well as how the tests should be interpreted.

Within the family, the first person to undergo genetic testing usually is the person who clearly has the disease (e.g., with numerous colon polyps with or without colon cancer). If genetic testing of this family member reveals a mutation responsible for a hereditary colon cancer syndrome, then other family members can be tested for the same mutation. Those family members who do not carry the mutation can be assured that they have not inherited the syndrome, whereas those who have the mutation should begin early screening for colon and other cancers. Depending on which syndrome is present and the age of the patient, removal of the colon may be recommended.