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Adenomatous polyposis syndromes are hereditary colorectal cancer syndromes that are associated with multiple adenomatous polyps in the colon. There are three adenomatous polyposis syndromes: familial adenomatous polyposis (FAP) and attenuated FAP (AFAP), which are caused by a mutation in the adenomatous polyposis coli ( APC ) gene, and MYH -associated polyposis (MAP), which is associated with mutations in the mutY homolog (MYH) gene.
FAMILIAL ADENOMATOUS POLYPOSIS (FAP)
Classical AFAP, which includes variations such as Gardner 's syndrome and Turcot's syndrome, is characterized by hundreds to thousands of adenomatous polyps located throughout the colon.23 In patients with FAP, these polyps tend to occur at an early age and are almost inevitable. Without intervention (i.e. with colectomy), nearly all patients with FAP will be diagnosed with colorectal cancer by age 50.26 Additionally, the majority of these patients are at-risk to develop adenomatous polyps and cancer in the upper gastrointestinal tract as well.52
ATTENUATED FAMILIAL ADENOMATOUS POLYPOSIS (AFAP)
AFAP is
a hereditary colorectal
cancer syndrome that can be differentiated from FAP because
it is typically associated with a far less dramatic proliferation
of polyps (usually ten to 99
cumulative adenomas).55 These
polyps are often located in the proximal colon (right side), with an average
age of onset much later than that of classical FAP.25 As
in FAP, upper gastrointestinal tract polyps (specifically in the stomach and
the duodenum) are common in AFAP and an increased risk of cancer in these areas
is seen as well.52
Since the majority of polyps associated with AFAP are located in the proximal colon, it may be difficult to distinguish AFAP from hereditary nonpolyposis colorectal cancer (HNPCC).27 A diagnosis of AFAP may be considered in patients who are suspicious for HNPCC but have tested negative for HNPCC germline mutations. Likewise, a diagnosis of HNPCC may be considered in patients suspicious for AFAP who test negative for APC germline mutations.
MYH-ASSOCIATED POLYPOSIS (MAP)
MAP is a hereditary colorectal cancer syndrome characterized by "multiple" colon polyps. Individuals with MAP have a wide range of polyposis, some having less severe polyposis (as in AFAP) and some appearing more like FAP with hundreds of polyps.56, 57 Due to the autosomal recessive pattern of inheritance, patients with MAP often have no family history of colon cancer or polyps in parents or children, although siblings may be affected.58
A patient's personal and/or family medical history can reveal that a predisposition to disease exists. When assessing hereditary cancer risk, a patient's comprehensive family history remains essential in determining the risk for adenomatous polyposis syndromes. However, it is important to remember that a patient with one of these syndromes may completely lack any family history of colorectal polyps and cancer. Twenty to 30 percent of FAP cases are estimated to be caused by de novo mutations; therefore, there may be no family history.31 Additionally, due to the autosomal recessive inheritance pattern of MAP, many affected patients will have no relatives with colorectal polyps or cancer.58 Genetic testing is the only way to distinguish family members who are truly at risk for these syndromes before intensive screening is instituted.
» Identifying Patients at Risk for Adenomatous Polyposis
Syndromes
A genetic test for adenomatous
polyposis syndromes
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