Genes are instructions for how the body grows and functions. Our genes are inherited (passed down) from our parents. Some genes help determine traits like hair color or eye color. Other genes may increase or decrease the chance of disease, such as developing polyps.

Some polyposis syndromes are caused by having a mutation (harmful genetic change) in a gene that is important for preventing polyp development. However, not all polyposis has a genetic cause that we know of. There are many other factors that may also promote polyp growth such as certain bacteria that lives in your colon, behaviors such as smoking, and potentially environmental exposures

There are many examples of situations when genetic testing is recommended for individuals with multiple polyps. Some examples include:

• Multiple (10 or more) adenomatous polyps of the colon
• Hamartomatous gastrointestinal polyps
• Multiple serrated polyps of the colon

If you need to be evaluated to potentially undergo genetic testing for a polyposis syndrome, this can be performed through our Gastrointestinal Cancer Risk Evaluation Program.

FAP is the most common hereditary polyposis syndrome and results from a mutation (change) in the APC gene. FAP is autosomal dominant, meaning that it can be passed from generation to generation and affects both men and women. FAP can also occur in people who have no family history of polyps or FAP (due to a new, de novo mutation that arises in the first person affected in the family with FAP).

There are two types of FAP: Classic FAP, which is associated with hundreds to thousands of colon polyps, and Attenuated FAP (AFAP), which is a milder form of FAP usually associated with fewer polyps that develop at later ages. Colon polyps can develop in the teenage years in Classic FAP, and FAP/AFAP is associated with a very high risk of colon cancer, if left untreated. Some ways to prevent colon cancer can include frequent colonoscopies with removal of polyps or surgery to remove the colon (colectomy) when too many polyps are present to remove individually.

Individuals with FAP can also have:

• Polyps in the stomach, including fundic gland polyps
• Polyps (adenomas) in the small intestine, particularly in the duodenum (the first part of the small intestine)
• Adenomatous changes of the ampulla (where the bile ducts from the liver and the pancreatic duct empty into the small intestine)
• Bony growths of the skull and jaw, called osteomas
• Cysts on the skin, called epidermoid cysts
• Extra teeth or dental abnormalities
• Tumors found in the abdomen, called desmoid tumors
• Freckle-like spots on the inside of the eye, called Congenital Hypertrophy of Retinal Pigment Epithelium (CHRPE

FAP can also be associated with cancers outside of the colon, including the duodenum, stomach, and thyroid. In order to lower cancer risks, there are multiple options that your doctor will discuss with you on an individual basis, including ongoing clinical studies investigating new medications for FAP. Most importantly, it is important that individuals with FAP be followed closely in a risk management program to ensure that their individualized cancer risk is being appropriately followed.

MUTYH-associated polyposis, also referred to as MAP, is a hereditary colonic polyposis syndrome caused by mutations (changes) in the MUTYH genes. Having one mutation in MUTYH occurs in 1-2% of the population. However, having only a single mutation in the MUTYH gene is not believed, at this time, to significantly increase the risk of developing cancer. MAP, on the other hand, results when an individual has two mutations in the MUTYH gene (one mutation from the mother and one mutation from the father). This is called autosomal recessive inheritance. Individuals with MAP often develop colon polyps early in life, even in their 20s, and these individuals have a significantly increased risk of colon cancer if left untreated. It is possible that they may have increased risks of other cancers as well in addition to colon cancer, and therefore all individuals with MAP should be closely followed in a risk management program with expertise in MAP.

Hamartomas are rare polyps that can develop throughout the gastrointestinal tract. While isolated hamartomas can be seen, developing multiple hamartomatous polyps throughout the GI tract raises concern for a hereditary polyposis syndrome. The three most common hamartomatous polyposis syndrome include Peutz-Jeghers, Juvenile Polyposis, and Cowden (also known as PTEN Hamartoma Tumor Syndrome) syndrome. However, all of these conditions are rare in the general population. These syndromes are associated with increased gastrointestinal cancer risk, in addition to other risks outside of the gastrointestinal tract. Genetic testing, endoscopic surveillance, and continued follow-up with a specialized risk management program is recommended for all individuals with a hamartomatous polyposis syndrome.

Serrated polyposis syndrome (SPS) is being identified more frequently. This syndrome is diagnosed based on the total number of serrated polyps (a specific type of polyp) an individual has throughout their lifetime. While some SPS is thought to be familial, a small number of individuals may carry mutations in a newly described gene called RNF43. However, the majority of SPS is considered to be sporadic (meaning it does not run through families). At this time it is believed that SPS increases the risk of colon cancer, however at this time SPS is not known to be associated with any increased cancer risks outside of the colon. Individuals with SPS should be followed by a program with expertise in the management of SPS.

Colonic adenomatous polyposis of unknown etiology is defined as having a cumulative total of 20 or more adenomas of the colon over the course of one's lifetime with negative genetic testing (meaning that genetic testing did not find any mutations explaining why the individual has polyps). Recommendations for managing these individuals are changing over time, but we know they may require more frequent colonoscopy given the increased risk of colon cancer. It is unclear if other cancer risks are associated with colonic adenomatous polyposis of unknown etiology, therefore individuals with this condition should be managed in a specialized program with expertise in polyposis.