MUTYH-Associated Polyposis (MAP)

2006-06-01   Benedetta Toschi , Maurizio Genuardi 

Department of Clinical Pathophysiology, University of Florence, Viale Gaetano Pieraccini 6, 50139 Firenze, Italy



MUTYH-Associated Polyposis (MAP)


MYH associated polyposis


MAP is a recently described condition predisposing to colorectal cancer, caused by germline mutations in the base excision repair (BER) gene MUTYH (MYH). The first description of an affected family was provided in 2002.


Autosomal recessive. Heterozygote frequency in the general population is currently estimated as 0.01-0.02.




247798 MUTYH-related attenuated familial adenomatous polyposis




Phenotype and clinics

The phenotype is often undistinguishable from that of autosomal dominant familial adenomatous polyposis (FAP) caused by mutations in APC gene. The number of adenomas is often lower in MAP (from 5 to more than 100), and affected patients are often sporadic cases. Biallelic MUTYH mutations have also been detected in patients affected with early-onset colorectal cancer (CRC) without polyps and in one with more than 1000 polyps. Cancers are more frequently located in the proximal side of the colon compared to APC-related FAP. Generally, mean age at diagnosis of MAP is 48-56 years, later than in APC-related FAP. A number of extracolonic manifestations have been observed, although their incidence is not yet well established. These include manifestations that are also associated with APC-related FAP, such as duodenal polyposis, duodenal cancer, osteomas, dental cysts and congenital hypertrophy of the retinal pigment epithelium. Breast cancer and thyroid cancer, and cutaneous tumors (pilomatricomas and sebaceous gland tumors) have also been reported.

Neoplastic risk

Penetrance of CRC is approximately 100% by age 65 years. Approximately 50% of patients present with CRC at the time of diagnosis. CRC risk in heterozygotes is not defined: some authors believe that monoallelic mutations may act as low penetrance alleles, increasing CRC risk, but larger studies with sufficient statistical power are necessary to accurately estimate the magnitude of such risk, if any.


No specific screening guidelines have yet been established. Periodic colonoscopy of the entire colon should be offered to biallelic mutations carriers. Prophylactic colectomy should be considered when number, size and\/or dysplasia of the polyps make continued surveillance unmanageable. Upper gastrointestinal surveillance is also indicated. Parents and children of individuals with biallelic mutations are obligate carriers of at least one MUTYH mutation. A baseline colonscopy has been suggested for these carriers, and, if findings are negative, screening should be repeated every 3-5 years.

Genes involved and Proteins


MYHMYHbetaMutYhomolog (hMYH)MutY (E.Coli) homologmutY homolog


MUTYH glycosylase


MUTYH is a DNA glycosylase that plays a key role in BER-mediated removal of 8-oxoG:A mismatches.


Most reported mutations in this gene cause production of a nonfunctional or low-functioning glycosylase enzyme. The two most common mutations in Caucasians, accounting for about 75%-80% of mutant alleles, are Y165C (or Tyr165Cys) and G382D (or Gly382Asp).


Pubmed IDLast YearTitleAuthors
118189652002Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors.Al-Tassan N et al
165575842006MUTYH-associated polyposis: 70 of 71 patients with biallelic mutations present with an attenuated or atypical phenotype.Aretz S et al
156904002005A kindred with MYH-associated polyposis and pilomatricomas.Baglioni S et al
155230922004Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk.Croitoru ME et al
129371242003Proportion and phenotype of MYH-associated colorectal neoplasia in a population-based series of Finnish colorectal cancer patients.Enholm S et al
159315962005Germline susceptibility to colorectal cancer due to base-excision repair gene defects.Farrington SM et al
149915772004Comprehensive analysis of the contribution of germline MYH variation to early-onset colorectal cancer.Fleischmann C et al
149997742004Prevalence of the Y165C, G382D and 1395delGGA germline mutations of the MYH gene in Italian patients with adenomatous polyposis coli and colorectal adenomas.Gismondi V et al
127070382003Germline mutations but not somatic changes at the MYH locus contribute to the pathogenesis of unselected colorectal cancers.Halford SE et al
157618602005Mutation analysis of the MYH gene in an Australian series of colorectal polyposis patients with or without germline APC mutations.Kairupan CF et al
159325532005Is prophylactic colectomy indicated in patients with MYH-associated polyposis?Leite JS et al
146336732003Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway.Lipton L et al
161409972005Multiplicity in polyp count and extracolonic manifestations in 40 Dutch patients with MYH associated polyposis coli (MAP).Nielsen M et al
162072122005Attenuated familial adenomatous polyposis and Muir-Torre syndrome linked to compound biallelic constitutional MYH gene mutations.Ponti G et al
160425732005MutYH (MYH) and colorectal cancer.Sampson JR et al
126067332003Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH.Sieber OM et al
159519632005A comparison of the phenotype and genotype in adenomatous polyposis patients with and without a family history.Truta B et al
151881612004High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis.Venesio T et al
152361662004MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps.Wang L et al
159435552005Germline mutations in the MYH gene in Swedish familial and sporadic colorectal cancer.Zhou XL et al

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