MUTYH Gene Mutations

MUTYH-associated Polyposis Syndrome (MAP)

MUTYH ASSOCIATED CANCER RISKS

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Additional Information

MUTYH Monoallelic gene

Associated Syndrome Name: MUTYH-associated Colorectal Cancer Risk

MUTYH Monoallelic Summary Cancer Risk Table

Cancer Genetic Cancer Risk
ColorectalElevated Risk

MUTYH Monoallelic gene Overview

MUTYH-associated Colorectal Cancer Risk 1, 2, 3, 4, 5
  • Individuals with a single MUTYH mutation (monoallelic MUTYH) may have a small increased risk for colorectal cancer. This increase in risk seems to be seen most consistently in patients who have a close relative (parent, brother, sister or child) who has had colorectal cancer, with increases in risk that are roughly equal to those associated with family history alone.
  • Individuals with mutations in both of their copies of the MUTYH gene (biallelic mutations) have a condition known as MUTYH-associated polyposis (MAP), which is associated with a high risk for cancer. This patient does not have a diagnosis of MAP, but may have relatives who are at risk for this condition. Please see the Information for Family Members section below for details.
  • Although there may be an increased risk for colorectal cancer for patients with a single MUTYH mutation, it may be possible to reduce this risk with appropriate medical management. The National Comprehensive Cancer Network (NCCN) has provided screening recommendations to address this risk. These guidelines will evolve as we learn more, and therefore it may be useful for patients with a single MUTYH mutation to be managed by a multidisciplinary team with expertise in medical genetics and the care of patients with hereditary cancer syndromes.

MUTYH Monoallelic gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
ColorectalTo age 801, 2, 3, 4, 63.4% to 10%3.0%

MUTYH Monoallelic Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
(Unless otherwise indicated by findings)
ColorectalCurrently there are no medical management guidelines for colorectal cancer risk in patients with a single MUTYH mutation unless colorectal cancer has been diagnosed in a first-degree relative3NANA

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the MUTYH Monoallelic gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

This patient carries a single MUTYH mutation (monoallelic). This patient's relatives are at risk for carrying a single MUTYH mutation, or mutations in both copies of MUTYH (biallelic). A single MUTYH mutation can lead to an increased risk for colorectal cancer. Relatives who have inherited mutations in both copies of MUTYH are at risk for MUTYH-associated Polyposis syndrome (MAP), with a 43%-100% risk of colorectal cancer risk to age 80 and a 5% risk for small bowel cancer. Genetic testing may be appropriate for close family members to determine whether they are at an increased risk for colorectal and other cancers.

References

  1. Jones N, et al. Increased colorectal cancer incidence in obligate carriers of heterozygous mutations in MUTYH. Gastroenterology. 2009 137:489-94 PubMed PMID: 19394335.
  2. Win AK, et al. Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer. Gastroenterology. 2014 146:1208-11. PMID: 24444654.
  3. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 3.2019. Dec 13. Available at http://www.nccn.org.
  4. Jenkins MA, et al. Risk of colorectal cancer in monoallelic and biallelic carriers of MYH mutations: a population-based case-family study. Cancer Epidemiol Biomarkers Prev. 2006 15:312-4. PMID: 16492921.
  5. Nielsen M, et al. MUTYH-Associated Polyposis. 2019 Oct 10. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available from http://www.ncbi.nlm.nih.gov/books/NBK107219/ PMID: 23035301.
  6. Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. https://seer.cancer.gov/faststats. (Accessed on 1-2-2017)
Last Updated on 10-Dec-2020

MUTYH Biallelic gene

Associated Syndrome Name: MUTYH-associated Polyposis syndrome (MAP)

MUTYH Biallelic Summary Cancer Risk Table

Cancer Genetic Cancer Risk
ColorectalHigh Risk
OtherHigh Risk

MUTYH Biallelic gene Overview

MUTYH-associated Polyposis syndrome (MAP) 1
  • Individuals with mutations in both copies of the MUTYH gene (biallelic mutations) have a condition called MUTYH-associated Polyposis syndrome (MAP).
  • Most patients with MAP have between 10 and 100's of colorectal polyps by a mean age of 50. These polyps are primarily adenomas, leading to a high risk for colorectal cancer. Colorectal cancer is sometimes diagnosed in individuals with no past history of polyps.
  • Patients with MAP also have an increased risk for cancer of the small bowel. Although the absolute risk is estimated to be only 5%, between 17% and 25% of patients with MAP will have duodenal polyps and consideration of upper endoscopy is recommended. Eleven percent of patients with MAP will have gastric polyps, but there does not appear to be any increased risk for gastric cancer.
  • Some studies have described a possible increased risk for a wide range of cancers and non-cancer findings in patients with MAP. However, these studies are not conclusive and the estimated risks are not large. For these reasons, there are no medical management guidelines to address these risks.
  • Although the risk for colorectal cancer in patients with MAP is very high, it is possible to reduce this risk with appropriate medical management. Guidelines for the management of patients with MAP have been developed by the National Comprehensive Cancer Network (NCCN). These are listed below. It is recommended that patients with MUTYH mutations and a diagnosis of MAP be managed by a multidisciplinary team with expertise in medical genetics and the care of patients with hereditary gastrointestinal cancer syndromes.

MUTYH Biallelic gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
ColorectalTo age 801, 243%-100%3.0%
Small BowelTo age 802, 35%0.2%

MUTYH Biallelic Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
(Unless otherwise indicated by findings)
ColorectalColonoscopy325 to 30 yearsEvery 1 to 2 years
Colorectal surgical evaluation and counseling.3, 4, 5Based on cancer diagnosis and/or polyp number, size and histologyNA
Small BowelConsider upper endoscopy, including complete visualization of the ampulla of Vater330 to 35 yearsEvery 4 years

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the MUTYH Biallelic gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

Since this patient has mutations in both copies of the MUTYH gene, it is almost certain each of their parents and all of their children carry at least one of these MUTYH mutations. Brothers and sisters are at very high risk for carrying either one or two MUTYH mutations. Since even a single MUTYH mutation can lead to an increased risk for cancer, it is especially important that this information be shared within the family and relatives talk with a healthcare provider about testing. The cancer risk tables that follow provide cancer risks for men and women with mutations in either one (monoallelic) or both (biallelic) copies of the MUTYH gene.

References

  1. Nielsen M, et al. MUTYH-Associated Polyposis. 2019 Oct 10. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available from http://www.ncbi.nlm.nih.gov/books/NBK107219/ PMID: 23035301.
  2. Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. https://seer.cancer.gov/faststats. (Accessed on 1-2-2017)
  3. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 3.2019. Dec 13. Available at http://www.nccn.org.
  4. Syngal S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 110:223-62. PMID: 25645574.
  5. Achatz MI, et al. Cancer Screening Recommendations and Clinical Management of Inherited Gastrointestinal Cancer Syndromes in Childhood. Clin Cancer Res. 2017 23:e107-e114. PMID: 28674119.
Last Updated on 10-Dec-2020