MUTYH-associated polyposis

What Does It Mean to Test Positive for a MUTYH Mutation?

The implications of MUTYH mutations depend on whether an individual has one or two mutations in the MUTYH gene.

If only one mutation is identified, the result on the first page will say "Positive: Carrier." Individuals with one MUTYH mutation, or carriers, likely have a moderately increased risk for colon cancer compared to the general population. The exact risk is unknown but studies show the risk for colon cancer may be approximately 5-8% over one's lifetime compared to approximately 4% in individuals who do not have a MUTYH mutation. This risk may be higher for MUTYH mutation carriers who also have a family history of colon cancer. Recommended cancer screening for carriers includes colonoscopy every five years beginning at age 40, or 10 years earlier than the youngest age of colorectal cancer diagnosis in a first-degree relative.

If two mutations are identified, the result on the first page will say "Positive: Individual at risk for disease." Individuals with two MUTYH mutations are said to have "MUTYH-associated polyposis" and are at significantly increased risk of developing colon cancer. This is because MUTYH mutations result in the development of numerous benign tumors, or polyps, within the lining of the intestine and colon. These pre-cancerous growths are known as "adenomas" and can develop into cancer if not removed. The remainder of this report is only applicable to individuals with two mutations.

What Are the Cancer Risks Associated with Two MUTYH Mutations?

MUTYH-associated polyposis (MAP) is primarily associated with an increased risk for colon and intestinal (small bowel) cancer. Other cancers, such as ovarian, bladder, breast, and uterine cancer, have been reported. However, individuals with MAP may have only a slightly greater risk for these other cancers compared to the general population. Individuals with MAP also have an increased risk for thyroid disease and possibly for the development of growths on the skin known as sebaceous gland tumors.

Cancer Risks and Average Ages of Onset

Most individuals with MUTYH-associated polyposis (MAP) have between 10 and hundreds of colon and/or intestinal polyps by age 50. If colonoscopies are not performed to remove pre-cancerous polyps, cancer will develop by age 65 in nearly 100% of affected individuals. 17-25% of individuals affected with MAP develop adenomas, or precancerous polyps, in the small intestine, which can develop into intestinal cancer if not removed.

As discussed above, other cancers, such as gastric (stomach), ovarian, bladder, breast, and uterine cancer have been reported in individuals with MAP. However, more research is needed to determine whether a true association exists and to determine exact cancer risks.

What Cancer-Screening or Risk-Reducing Options Are Available?

The most important aspect of management of an individual with two MUTYH mutations is increased cancer screening, to allow the earliest possible detection of any tumors. Early detection and removal of adenomas (precancerous colon polyps) can significantly reduce a MUTYH mutation carrier's risk of developing colon cancer. Specifics of screening may vary depending on the individual's family and personal history.

For Men and Women:

• Annual physical examinations are recommended.
• Colonoscopies are recommended beginning at age 25-30. It is recommended to repeat colonoscopy every 2-3 years, or more frequently based on previous findings.
• Upper endoscopy should be considered beginning at age 30-35. It is recommended to repeat upper endoscopy every 3-5 years, or more frequently based on previous findings.
• Surgical removal of the colon may be considered if polyps cannot be managed with regular colonoscopies. This procedure is known to dramatically reduce, if not prevent, the risk of developing colon cancer.
• For those who undergo removal of the colon, endoscopy of any remaining intestinal tissue is recommended every 6 to 12 months.

There are currently no screening or prevention guidelines specific to the other potential cancer risks associated with MAP.

What Is the Chance That Family Members of Individuals with Two MUTYH Mutations Have the Same Mutation?

MUTYH mutations are passed down in a family in a recessive manner. In order to be affected with MAP, a person must inherit two mutations in the MUTYH gene, one from each parent. For this reason, it is important for MUTYH carriers to discuss genetic test results with family members.

• Each parent of an individual with MAP will likely be a carrier for one MUTYH mutation and have a moderately increased risk for colon cancer.
• Siblings have a one-in-four (25%) chance of having two mutations and being affected with MAP. Siblings also have a one-in-two (50%) chance of having one mutation in MUTYH, causing a moderately increased risk for colon cancer.
• Children of an individual who has two mutations in MUTYH will inherit one MUTYH mutation from their affected parent and will be MUTYH carriers. Children will only be at risk to have MAP, and a high risk to develop colon cancer if their other parent also carries a MUTYH mutation. For this reason, individuals who are affected with MAP may consider carrier screening for MUTYH mutations in their spouse or partner.
• More distant relatives, such as aunts, uncles, grandparents, and cousins, also have a chance of having a MUTYH mutation. This is true for relatives on both sides of the family.

Keep in mind that having one MUTYH mutation, or being a carrier, is different than having two mutations and being affected with MAP. Individuals with one MUTYH mutation, or carriers, may have a moderately increased risk for colon cancer (approximately 5-8% lifetime risk) compared to the general population (approximately 4% lifetime risk).