Patients that form colon adenomas more often than the general population may have an adenomatous polyposis syndrome. These are hereditary colorectal cancer syndromes caused by mutations in one of two genes: the APC gene or the MYH gene. The numerous adenomas found in these patients lead to an increased risk of colorectal cancer.

APC Gene Mutations

Individuals who have an APC mutation have up to a 100% lifetime risk of colorectal cancer. APC is the gene responsible for both classic FAP and attenuated FAP (AFAP).

Classic FAP is characterized by the presence of hundreds to thousands of adenomatous colonic polyps, and without intervention, colorectal cancer is inevitable. Screening for classic FAP begins in childhood, between the ages of 10-12 years, with an annual flexible sigmoidoscopy. Once adenomatous polyposis is detected, prophylactic total colectomy is recommended. It is also important to recognize that 20%-30% of FAP cases may be caused by a de novo mutation. This means that there may be no prior family history of colon polyps or cancer. Genetic testing remains important for these patients because they can pass the APC mutation on to their children.

Attenuated FAP (AFAP) is also caused by mutations in the APC gene. Individuals with AFAP have an 80%-100% lifetime risk of developing colorectal cancer. However, AFAP is generally associated with fewer colon polyps (usually 10-99 cumulative adenomas, although AFAP has been diagnosed in patients with less than 10 polyps) and a preponderance of proximal (right-sided) polyps. For these reasons, AFAP may be difficult to distinguish from HNPCC without genetic testing. Specific screening recommendations for AFAP patients include colonoscopy every 1-3 years beginning in the late teens to early twenties. Unlike classic FAP, prophylactic colectomy may not be necessary for all patients. AFAP patients should be managed according to their polyp burden.

Mutations in APC are inherited in an autosomal dominant pattern. First degree relatives are at 50% risk to carry the same mutation. Once a mutation has been detected in a family, other family members can be tested for the specific family mutation. Those family members testing positive for the known mutation are managed more aggressively. By contrast, individuals who do not inherit the family mutation may adhere to general population screening guidelines.

MYH Gene Mutations

Another hereditary explanation for multiple adenomatous polyps is a condition called "MYH-associated polyposis" or MAP. Individuals with MAP have mutations in both of their MYH genes (one from each parent, often referred to as "biallelic MYH mutations"). Due to the association of MAP and multiple adenomas, the colorectal cancer risk is thought to be significantly elevated, although the exact risk is unknown. MAP has been diagnosed in patients with very few polyps (0 to 9) but is more likely in patients with 10 or more cumulative colon adenomas. MAP patients may also present with up to 1000 colon adenomas, like classic FAP patients. As in FAP and AFAP, a diagnosis of this condition allows for increased surveillance at the appropriate age. Genetic testing is available to accurately identify patients with mutations in the MYH gene.

Unique screening recommendations for MAP have not yet been established. It is recommended that patients with MAP follow screening guidelines for FAP or AFAP, depending on the individual polyp burden.

Mutations in MYH are inherited in an autosomal recessive pattern. For this reason, there is often a lack of "polyp formers" in the family history. When a patient has been diagnosed with biallelic MYH mutations, his parents are likely "carriers" of a single MYH mutation. In most cases, children of individuals with MAP will be "carriers" as well. Siblings of the patient are at 25% risk to carry the same two MYH mutations.

Once MYH mutations have been detected in a family, other family members can be tested for these specific family mutations. As in FAP and AFAP, those family members testing positive for both MYH mutations are managed more aggressively. Those without MAP may adhere to general population screening guidelines. It is possible that MYH mutations may explain some cases of FAP or AFAP that appear to be de novo.

Individuals who should be offered genetic testing for adenomatous polyposis syndromes are:

	Individuals who are clinically affected with FAP (100 colorectal adenomas)
	Individuals with "multiple" cumulative colorectal adenomas
		Note: AFAP and MAP have been diagnosed in patients with very few polyps (0 to 9), although these conditions are more likely in patients with 10 or more cumulative adenomas.
	Relatives of APC or MYH mutation carriers, as appropriate

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