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MUTYH-associated polyposis

Shilpa Grover, MD, MPH
Elena Stoffel, MD, MPH
Section Editor
J Thomas Lamont, MD
Deputy Editor
Anne C Travis, MD, MSc, FACG, AGAF


MUTYH-associated polyposis is an autosomal recessive polyposis syndrome. Affected patients have multiple colorectal adenomas and an increased risk of colorectal cancer. This topic will review the clinical manifestations, diagnosis, and management of MUTYH-associated polyposis. The clinical manifestations, diagnosis, and management of familial adenomatous polyposis, Lynch syndrome, and hamartomatous polyposis syndromes are discussed elsewhere. (See "Clinical manifestations and diagnosis of familial adenomatous polyposis" and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Screening and management" and "Juvenile polyposis syndrome".)


MUTYH-associated polyposis is an autosomal recessive polyposis syndrome caused by biallelic mutations in the MUTYH gene [1]. MUTYH is a base excision repair gene whose protein repairs oxidative damage to the DNA. Oxidation of guanine leads to the formation of 8-oxo-6, 7, 8-dihydroxy-2 deoxyguanosine. Failure of base excision repair results in mispairing of this nucleotide with adenine and resultant somatic CG–AT transversions in multiple genes, including the APC and KRAS genes. The target genes that are mutated as a consequence of oxidative damage strongly influence the polyposis phenotype [2].

The two most common MUTYH gene mutations in Western Europeans and North Americans are Y179C and G396D (previously referred to as Y165C and G382D, respectively) [3]. However, mutations at different loci have been reported in other populations [4-8]. Patients with MUTYH-associated polyposis may be homozygous or compound heterozygous for these or other mutations in the MUTYH gene.


Monoallelic MUTYH mutations are found in 1 to 2 percent of the general population, with biallelic mutations identified in <1 percent of individuals diagnosed with colorectal cancer [9]. Among individuals with multiple colorectal adenomas in whom an APC mutation has been excluded, biallelic MUTYH mutations are found in 7 to 13 percent of patients with >100 adenomas and in 14 to 40 percent of patients with 10 to 99 adenomas [1,10-13].


MUTYH-associated polyposis is typically characterized by the presence of multiple colorectal adenomas; however, the phenotype can vary. A number of extracolonic manifestations have also been associated with MUTYH-associated polyposis.


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Literature review current through: Sep 2016. | This topic last updated: Jun 16, 2016.
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