MUTYH-associated polyps

MUTYH-associated polyposis (or MAP) is a rare disorder that runs in families and tends to form polyps in the colon and rectum. The presence of these polyps greatly increases the risk of developing colorectal cancer. If you’re among those affected by this condition, be sure to work with your care team for advice on how to lower this risk.

What is MUTYH-associated polyposis?

MAP is a type of hereditary polyposis known to cause multiple polyps—though the number can range by patient, from fewer than 20 to hundreds, according to the American Society of Clinical Oncology. It shares similarities with other hereditary conditions such as familial adenomatous polyposis (FAP) and attenuated familial adenomatous polyposis (AFAP).

People with MAP typically develop polyps (usually fewer than 100) on the inner walls of the colon and rectum, though some may appear in the stomach and small intestine.

Polyps are abnormal growths that occur on mucous membranes. Most are benign, but some can turn into cancer. The likelihood that a polyp becomes cancerous depends on the type, location and size—in addition to any genetic predispositions to polyps and cancers you may have.

Polyps associated with MAP almost always become cancerous if left untreated. That’s why, if you have MAP, it’s important to have your polyps removed.

Symptoms of MUTYH-associated polyposis

Colorectal polyps don't typically cause many symptoms, but some people may have:

• Bloody stool
• Changes in stool
• Fatigue from blood loss

Patients with MAP are also more likely to develop other types of growths.

Other growths that occur more often in MAP patients include:

• Lumps on the thyroid gland
• Benign growths on the adrenal glands
• Dental abnormalities, including jawbone cysts
• Benign growths inside the eye called congenital hypertrophy of the retinal pigment epithelium

Causes of MUTYH-associated polyposis

MAP is caused by a genetic change, or mutation, in the MUTYH gene.

Your genes contain information that your cells use to create proteins, which perform different functions in the body. Each time a cell divides, it makes a copy of all of its genes. When these gene copies are made, they sometimes contain mutations that cause a gene not to work as well (or at all). These mutations also can lead to the development of polyps and cancer.

MAP mutations are inherited in an autosomal recessive manner, which means both copies of the MUTYH gene need to have mutations in order for the condition to develop. Your likelihood of inheriting this mutated gene depends on your parents. Both of your parents need to have at least one mutated copy of MUTYH and pass it on for you to have any chance of inheriting this condition.

You can also pass MAP on to your children, depending on whether the MUTYH gene is mutated in you and your partner.

• If you have MAP (two mutated MUTYH genes) and your partner has one mutated MUTYH gene, your chance of having a child with MAP is 50 percent.
• If you and your partner each have one mutated MUTYH gene, your child’s chance of having MAP is 25 percent.
• If your partner has no mutated MUTYH genes and you have one mutated MUTYH gene (or vice versa), then none of your children will develop MAP, although they could be carriers.

MUTYH-associated polyposis risk factors for cancer

The presence of MUTYH-associated polyps contributes to an increased risk of developing colorectal cancer. By age 60, people with MAP have a 43 percent to 63 percent chance of developing colorectal cancer, according to GeneReviews. The median age of onset for colorectal cancer in MAP patients is 48 years old. The lifetime risk of colorectal cancer in MAP patients is 80 percent to 90 percent, especially if you aren’t being regularly screened for polyps.

In addition, GeneReviews notes that MAP patients are at a higher lifetime risk for other cancers, including those of the:

• Gastrointestinal tract, including the stomach (1 percent) and duodenum (4 percent)
• Breast (12 percent to 25 percent), ovaries (6 percent to 14 percent) and endometrium (3 percent)
• Bladder (6 percent to 8 percent in women; 6 percent to 25 percent in men)
• Skin, pancreas and thyroid (possible increased risk)

Diagnosis of MUTYH-associated polyposis

Genetic testing is required to determine whether you have MAP. Your doctor will ask about your symptoms and family history.

Your doctor may suspect MAP if:

• You’re age 60 or younger and have had 10 or more colorectal adenomas
• You’ve had 20 or more colorectal adenomas at any age
• You’ve had at least five sessile serrated polyps near the last part of the colon (and two or more are larger than 10 mm), or more than 20 colon polyps of any size (excluding typically benign “hyperplastic” polyps that are found in the rectum and sigmoid colon)
• You have duodenal polyps or cancer

MUTYH-associated polyposis screenings

According to GeneReviews, patients with MAP should have regular screenings to monitor for the development of polyps and signs of cancer. These may include:

• Annual physical examination
• Colonoscopies every one to two years starting by age 25 to 30
• Upper endoscopy and duodenoscopy every three months to four years starting at age 30 to 35
• Regular thyroid ultrasounds
• Regular skin cancer screenings with a dermatologist

During endoscopic screening tests, suspicious polyps are identified and biopsied, and removed if necessary. If polyps grow too large or too dense, your doctor may recommend surgery to remove the affected part of the colon. Your care team may suggest a subtotal colectomy, which would remove the colon but not the rectum, or a proctocolectomy, which removes both the colon and rectum.