MUTYH (or MYH)-Associated Polyposis

Approved by the Cancer.Net Editorial Board , 01/2022

What is MUTYH (MYH)-associated polyposis?

MUTYH (MYH)-associated polyposis (MAP) is a hereditary condition. People with MAP tend to develop multiple adenomatous colon polyps during their lifetime and will have an increased risk of colorectal cancer if they are not monitored closely with regular colonoscopies . An adenomatous polyp is an area where the normal cells that line the inside of the colon begin to form a mass. At first, a polyp is benign, meaning it is noncancerous and will not spread. However, some polyps can eventually turn malignant, meaning cancerous, and cancers can spread to other parts of the body. It is likely that people with MAP will develop many polyps, and therefore their risk for colorectal cancer may be increased if these polyps are not removed.

In some people, MAP is associated with developing hundreds of polyps, and it appears to be similar to the other hereditary conditions of familial adenomatous polyposis (FAP) and attenuated familial adenomatous polyposis (AFAP) . In other cases, people with MAP can be diagnosed with fewer polyps (less than 20) and/or colorectal cancer at a young age.

Some people with MAP have an increased risk of developing polyps in the upper gastrointestinal tract, such as the stomach and small intestine. The risk of thyroid cancer may also be increased in individuals with MAP.

What causes MAP?

MAP is a genetic condition. This means that the risk of colon polyps and colorectal cancer can be passed from generation to generation in a family. Genetic alterations which disrupt the function of the MUTYH gene are known to cause MAP. This type of change to a gene can also be called a genetic mutation, gene alteration, pathogenic or likely pathogenic germline variant, or a disruptive gene change. (Note that MUTYH is also known as the MYH gene).

How is MAP inherited?

Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 inherited from the father. MAP follows an autosomal recessive inheritance pattern, in which mutation or alteration needs to be present in both copies of the MUTYH gene in order for a person to have an increased risk of getting that disease. This means that each parent must pass on this alteration for a child to be affected. A person who has only 1 altered copy of MUTYH is called a carrier. When both parents are carriers of a gene change associated with a recessive condition like MAP, there is a 25% chance that a child will inherit 2 altered copies of the gene, causing them to be affected with the disease. Individuals who carry only 1 altered copy of the MUTYH gene do not develop MAP.

Options exist for people interested in having a child when a prospective parent may carry a genetic change that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic variant to reduce the likelihood that their children will inherit the condition. A person's eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed and is tested for the hereditary condition in question. The parent(s) can then choose to transfer embryos which do not have the genetic variant. PGD has been in use for over 2 decades, and it has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.

How common is MAP?

Most colorectal cancer is sporadic, meaning it occurs by chance with no known cause. The percentage of colorectal cancer that can be attributed to MAP is unknown. It is estimated that as many as 1 in every 100 people may carry a single mutation in the MUTYH gene.

How is MAP diagnosed?

MAP is considered as a possible diagnosis when a person has multiple adenomatous colon polyps but does not have an alteration in the APC gene associated with FAP and AFAP. It may also be considered if someone has a brother or sister with multiple colon polyps, but there is no history of colon problems in previous generations. MAP is diagnosed when a person is found to have 2 alterations in the MUTYH gene. Although most individuals with MAP carry at least 1 of the 2 most common alterations in MUTYH ( Y165C and G382D), there are additional MUTYH alterations that can be detected by complete gene sequencing tests.

What are the estimated cancer risks associated with MAP?

Specific cancer risks associated with MAP have not been determined. The risk of colorectal cancer is considered to be significantly increased, and there may be an increased risk of other cancers of the gastrointestinal tract and thyroid gland as well.

What are the screening options for MAP?

ASCO recommends the following screening for people with MAP. It is important to discuss these options with your health care team, as each individual is different:

  • Colonoscopy every 1 to 2 years, beginning at age 25 to 30.

  • Once a person develops polyps, the colonoscopy frequency may be increased with the goal of removing all large polyps

  • If an individual with MAP develops colorectal cancer or if colon polyps are too numerous to be removed during a colonoscopy, surgery may be considered. Colectomy is the surgical removal of part or all of the colon. This may be considered if polyps cannot be managed with regular colonoscopies because there are too many.

  • Upper endoscopy (esophagogastroduodenoscopy or EGD) at age 25 to 30 or once colorectal polyps are detected, whichever occurs first

  • Ultrasound of the thyroid gland may be considered to screen for thyroid cancer, starting at age 25 to 30

Screening options may change over time as new technologies are developed and more is learned about MAP. It is important to talk with your doctor about appropriate screening tests.

Learn more about what to expect when having common tests, procedures, and scans , and read more about these screening recommendations at www.asco.org/endorsements/HereditaryCRC . (Please note this link takes you to another ASCO website.)

Questions to ask the health care team

If you are concerned about your risk of developing cancer, talk with your health care team. It can be helpful to bring someone along to your appointments to take notes. Consider asking the following questions:

  • What is my risk of colorectal cancer?

  • How many colon polyps have I had in total?

  • What type of colon polyps have I had? The 2 most common types are hyperplastic and adenomatous.

  • What can I do to reduce my risk of cancer?

  • What are my options for cancer screening?

If you are concerned about your family history and think your family may have MAP, consider asking the following questions:

  • Does my family history increase my risk of colorectal cancer?

  • Does it suggest the need for a cancer risk assessment? What does that mean?

  • Will you refer me to a genetic counselor or other genetics specialist?

  • Should I consider genetic testing ?