Etiology and Clinical Features of Adenomatous Polyposis Syndrome

The most common adenomatous polyposis conditions are thought to account for approximately 2% of all colon cancer.81,82. They can be categorized into three conditions: familial adenomatous polyposis, attenuated familial adenomatous polyposis and MYH-associated polyposis.

Classic familial adenomatous polyposis (FAP) and attenuated familial adenomatous polyposis (AFAP) are due to mutations in the adenomatous polyposis coli (APC) gene. The APC gene is a tumor suppressor gene which regulates cellular growth and proliferation. Both FAP and AFAP are inherited in an autosomal dominant manner.  MYH-associated polyposis (MAP) is caused by mutations in the mutY homolog (MYH) gene.  MAP is inherited in an autosomal recessive manner.  Individuals with MAP have mutations in both of their MYH genes (one from each parent, often referred to as “biallelic MYH mutations”).  Patients often have no family history of colon cancer or polyps in parents (although siblings may be affected)).83 The MYH gene is an important part of the base excision repair (BER) pathway, which allows for repair of DNA mutations caused by oxidative damage to cells. MAP is believed to account for approximately 1% of all colorectal cancers. MAP can cause patients to develop colorectal cancer even in the absence of colon polyposis.280

When assessing hereditary cancer risk, a patient’s personal and family history is collected to investigate the risk for a polyposis syndrome.  Once a patient is identified as being at increased risk for one of these syndromes, genetic test results provide the most accurate means of cancer risk assessment for a patient.  It is important to note that approximately 20% to 30% of FAP cases are caused by new mutations, meaning that an APC germline mutations may be present in an individual even if it is absent in both parents.84 Also, due to the autosomal recessive inheritance pattern of MAP, many affected patients have no relatives with colorectal polyps or cancer.83 Genetic testing is the only way to identify truly at-risk family members.