MYH-associated polyposis (MAP) is a rare, hereditary condition characterized by multiple adenomatous polyps in the colorectum. The known genetic cause is mutations (genetic changes) in the MYH gene. Individuals with MAP require lifelong gastrointestinal examinations and medical care by a health care team knowledgeable about MAP. This team may include gastroenterologists, surgeons, endocrinologists, primary care physicians, geneticists, genetic counselors, and oncologists. Individuals and families with MAP may find great benefit by joining a hereditary colon cancer registry.
Below you will find answers to the questions most frequently asked by individuals with MAP and their family members
What is MAP?
MYH is a gene involved in the repair of oxidative damage to the DNA. Oxidation causes changes in the DNA molecule that in turn affect many genes, including some genes responsible for regulation of cellular growth (such as the APC and KRAS genes). People with problems in the MYH gene can develop lots of different types of polyps in the large intestine, including adenomas, sessile serrated polyps and hyperplasic polyps. Most individuals with MAP usually develop between 10-100 polyps, although there have been some individuals with over 1,000 polyps. These polyps are often found in the late 40s. Individuals with MAP usually have fewer polyps than people with familial adenomatous polyposis (FAP). Because FAP and MAP appear similar, a detailed family history is important to help distinguish the two. MAP is different from other hereditary colorectal cancer syndromes because it is inherited in a recessive manner.
What Are The Cancer Risks Associated With MAP?
People with MAP are at an increased risk of developing colon and rectal cancer. The majority of colon cancers will occur between the fifth and seventh decade of life. An estimated 50% of people with MAP will have colorectal cancer at the time of diagnosis.
Are There Any Other Risks Associated With MAP?
Although MAP primarily affects the large intestine (colon) and rectum, the mutation is in every cell in the body and other organs can be affected. Patients can develop gastric fundic gland polyps (polyps in the stomach) and duodenal adenomas (polyps in the first part the small intestine); this risk is 4-25%. The fundic gland polyps are usually not pre-cancerous but the duodenal polyps, called adenomas, are pre-cancerous and may lead to duodenal cancer.
Based on some recent research, individuals with MAP are at an increased risk for developing thyroid disease or nodules on their thyroid that could develop into cancer. It is also suspected there is an increased risk to develop cancer of the kidneys.
How is MAP Diagnosed?
The diagnosis of MAP is suspected when multiple adenomatous polyps are found in the colon and rectum. MAP is suspected when an individual has greater than ten adenomatous colon or rectal polyps and does not have a mutation in the APC gene associated with FAP. MAP can also be considered if an individual has brothers or sisters with multiple colon polyps, but has no history of colon polyps or cancer in his or her parents.
Genetic counseling and genetic testing should be offered to anyone with a history described above. The gene MYH has been associated with MAP. Genetic testing, which involves a blood draw or obtaining a brushing from the inside of the mouth (buccal swab), can be done to determine if MYH mutations are present. MAP is diagnosed when a person is found to have two MYH gene mutations. In White individuals, the two most common mutations are Y165C and G382D. Once mutations are identified in an individual, his or her family members can be tested for that mutation.
How is MAP Inherited?
MAP is the only known syndrome of inherited colorectal cancer that is inherited in an autosomal recessive pattern. In recessive inheritance, both copies of the gene must be mutated for the disease to appear. Everyone has two copies of the MYH gene. Individuals with MAP have a mutation in each copy of the MYH gene. This means the mother and father of an individual with MAP each have one copy of the MYH with a mutation and are known as “carriers”. Carriers are not believed to have an increased risk of colorectal cancer or polyps. Approximately 1-2% of the population carries an MYH gene mutation.
The children of two mutation carriers have a 1 in 4 (25%) chance of having no MYH mutations. This person would be completely unaffected and could not pass any MYH mutations on to their children. There is a 2 in 4 (50%) chance of also being a carrier. These children would not MAP, but would have a chance of passing the one MYH mutation they have onto their own kids. Finally, there is a 1 in 4 (25%) of both MYH mutations being passed on, in which case this person would have MAP. All children of someone with MAP will have at least one MYH mutation.
Individuals diagnosed with MAP should inform their family members about their diagnosis and encourage their family members to undergo genetic counseling. This evaluation includes an evaluation of their personal history, exploration of the family history, and genetic testing for the MYH gene mutations identified in the family. Recommendations to keep the patient and his or her family healthy and to prevent cancer will also be provided.
How is MAP Treated?
Individuals with MAP are best monitored with colonoscopy starting at age 20 or 10 years prior the youngest diagnosis in the family, whichever is earlier. It is important that people with MAP have lifelong colonoscopies because new polyps can form that may turn into a cancer. If less than 20 polyps are found, they can be removed individually during a colonoscopy. If the polyps are too numerous or too fast growing, then surgical removal of the colon and/or rectum might be necessary. While the prospect of surgery may be upsetting, it is important to realize that without it, the risk of colorectal cancer is very high. The bowel is reconstructed by an ileorectal anastomosis (IRA) or a J pouch, so a permanent stoma (bag) is usually avoided.
The timing and choice of colon surgery depend on several factors, primarily the number and size of the polyps. Because MAP cannot be cured our aim is to prevent cancer but at the same time preserve a healthy, unaffected lifestyle for our patients. Laparoscopic surgery has made removal of the colon a lot less painful and a lot less disabling. Then the large intestine is checked yearly until surgery. Even after surgery the remaining bowel is checked yearly.
Certain non-steroidal, anti-inflammatory medications, such as sulindac have been shown to reduce, and may prevent, adenomatous colorectal polyps and can be considered for use in patient with MAP. The use of medications to prevent disease is called chemoprevention.
An upper endoscopy or an esophagogastroduodenoscopy (EGD) is also recommended beginning at age 20 and continue every 1-3 years, depending on the size, number and microscopic analysis of the duodenal polyp. All MAP patients should have a baseline thyroid ultrasound starting at the age of 20. This should be repeated yearly, or more frequently id abnormalities are detected.