Colorectal cancer

MUTYH-associated polyposis

From Cancer Guidelines Wiki

Background[edit source]

MUTYH-associated polyposis is a recessively inherited predisposition to adenomatous colorectal polyps and early onset colorectal cancer due to biallelic mutations in the MUTYH gene. Germline MUTYH mutations predispose to developing somatic APC mutations and the KRAS Gly12Cys ‘hotspot’ mutation in the gastrointestinal tract. Affected individuals commonly have between 20 and 100 adenomas but may have > 100.[1][2]

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Management[edit source]

No systematic reviews on this topic were undertaken in the development of this section. The guidance on MUTH-associated polyposis is based on recent international guidelines.[1][3][4][2] (See Guidelines Development for more information).

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Genetic testing[edit source]

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  • Referral to a genetics service for germline genetic testing for mutations in MUTYH is indicated for persons with a cumulative count of ≥ 20 colorectal adenomas at any age (Syngal et al., 2015). It is also indicated for siblings of a MUTYH biallelic mutation carrier (Syngal et al., 2015).

Testing may also be considered in patients with ≥ 10 adenomas and any of the following (Syngal et al., 2015) :

  • age under 50
  • synchronous colorectal cancer
  • both adenomatous and serrated polyps where the adenomatous polyps dominate
  • family history suggestive of recessive inheritance (e.g. consanguinity in parents or siblings with documented adenomatous polyposis or colorectal cancer).

Clinical practice in some familial cancer clinics would accept patients in these categories even if there are no synchronous adenomas in the proband.

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Surveillance and management[edit source]

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Biallelic mutation carriers should have colonoscopy every 2 years starting at age 18 to 20 years(Cancer Institute NSW, 2016; Robays and Poppe, 2014; Balmaña et al., 2013). If polyps are detected, annual colonoscopy may be required to control the polyp burden (Cancer Institute NSW, 2016). If polyps cannot be easily managed colonoscopically, a colectomy with ileorectal anastomosis should be considered and discussed with the patient (Cancer Institute NSW, 2016; Balmaña et al., 2013) The residual rectum requires annual surveillance.

Monoallelic MUTYH mutations are present in 1 to 2% of the population and may confer, on average, a 1.5- to 2-fold increase in the risk of colorectal cancer.[1] There is currently no consensus regarding surveillance and management, but an option may be to offer colonoscopy 5 yearly from 10 years younger than the earliest cancer diagnosis in the family.[1][2]

Next section: Lynch syndrome

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References[edit source]

  1. 1.0 1.1 1.2 1.3 Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 2015 Feb;110(2):223-62; quiz 263 Available from:
  2. 2.0 2.1 2.2 Balmaña J, Balaguer F, Cervantes A, Arnold D, ESMO Guidelines Working Group.. Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines. Ann Oncol 2013 Oct;24 Suppl 6:vi73-80 Available from:
  3. Cancer Institute NSW. eviQ Cancer Genetics Referral Guidelines for Colorectal Cancer or Polyposis Risk Assessment and Consideration of Genetic Testing. [homepage on the internet] Sydney; 2016 [cited 2016 Sep 6]. Available from:
  4. Robays J, Poppe B. Oncogenetic testing for Lynch syndrome and familial adenomatous polyposis. Brussels: Belgian Health Care Knowledge Centre (KCE); 2014.

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