Familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) are the two major hereditary colorectal cancer syndromes linked to a mutation in the adenomatous polyposis coli (APC) gene. MYH-associated polyposis (MAP) is a related syndrome linked to mutations in the mutY homolog (MYH) gene. Individuals with FAP have up to a 100% lifetime risk of developing colorectal cancer. Individuals with AFAP have an approximate 80% to 100% lifetime risk of developing colorectal cancer. The colorectal cancer risk for individuals with MAP has not been determined. Due to the association of MAP and multiple adenomas, the colorectal cancer risk is thought to be significantly elevated, although the exact risk is currently unknown.

	FAP and AFAP are the two major hereditary colorectal cancer syndromes linked to a mutation in the APC gene. MAP is a related syndrome linked to mutations in the MYH gene.

It is important to note that not all patients with FAP, AFAP, or MAP will have a family history of colorectal cancer or polyps. Although the majority of APC mutations are inherited, 20% to 30% of FAP cases are thought to be caused by de novo mutations, meaning that an APC germline mutation may be present in an individual even if it is absent in both parents. Additionally, MAP is inherited in an autosomal recessive pattern and most often, an individual affected with multiple polyps is a result of two unaffected "carrier" parents. Genetic testing is the only way to distinguish family members who are truly at risk for these syndromes before intensive screening is instituted.

FAMILIAL ADENOMATOUS POLYPOSIS (FAP)
Classical FAP, which includes variations such as Gardner's syndrome and Turcot's syndrome, is characterized by hundreds to thousands of adenomatous polyps (pre-cancerous tumors that can become malignant) located throughout the large intestine. These polyps develop at an early age; the average age of onset for colorectal adenomatous polyps in individuals with FAP is 16 years (range 7-36). By age 35, 95% of these patients will develop polyps. The majority of patients (50%-90%) with FAP develop adenomatous polyps in the upper gastrointestinal tract and are commonly found in the second and third portions of the duodenum. If left untreated (ie, colectomy) patients with FAP will develop colorectal cancer, typically at a much earlier age than the general population. Of those untreated patients with FAP, nearly all (93%) will develop colorectal cancer by age 50.

ATTENUATED FAMILIAL ADENOMATOUS POLYPOSIS (AFAP)
AFAP is a hereditary colorectal cancer syndrome caused by a mutation in the same APC gene responsible for FAP. This syndrome can be differentiated from FAP by the number of adenomatous colon polyps and the age at which these polyps generally develop. AFAP is typically associated with a far less dramatic proliferation of polyps (usually 10-99 cumulative adenomas, although AFAP has been diagnosed in patients with less than 10 polyps) compared to the hundreds to thousands of polyps associated with FAP. These polyps present with an average age of onset much later than that associated with classical FAP (44 years of age for AFAP vs 16 years of age for FAP). The average age of onset for colorectal cancer in individuals with AFAP is 56 years.

For patients with AFAP, the majority of polyps are located in the proximal colon (right side), which may make it difficult to distinguish AFAP from hereditary nonpolyposis colorectal cancer (HNPCC). Patients suspected of HNPCC who have tested negative for a HNPCC germline mutation, should be considered for genetic testing for AFAP. As in FAP, upper gastrointestinal tract polyps are common in individuals with AFAP, specifically in the stomach and the duodenum, and an increased risk of cancer in these areas is seen.

MYH-ASSOCIATED POLYPOSIS (MAP)
MAP is a hereditary colorectal cancer syndrome characterized by "multiple" adenomatous colon polyps. It is associated with mutations in the MYH gene and is often difficult to distinguish clinically from FAP and AFAP. MAP has been diagnosed in patients with very few polyps (0 to 9), although it is more likely in patients with 10 or more cumulative colon polyps. MAP patients may also present with up to 1000 colon adenomas like individuals with FAP. Due to the autosomal recessive pattern of inheritance, patients with MAP often have no family history of multiple polyps in parents or children, although siblings may be affected. The specific cancer risk, average age of onset, or location of polyps have not yet been established specifically for MAP. However, it is thought that patients with MAP should be managed according to guidelines developed for FAP or AFAP patients, depending on the individual polyp burden.

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