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MUTYH-Associated Polyposis (MAP)

Written2006-06Benedetta Toschi, Maurizio Genuardi
Department of Clinical Pathophysiology, University of Florence, Viale Gaetano Pieraccini 6, 50139 Firenze, Italy

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Other namesMYH associated polyposis
Atlas_Id 10092
Genes implicated inMUTYH  
Note 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.
Inheritance Autosomal recessive. Heterozygote frequency in the general population is currently estimated as 0.01-0.02.


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.
Treatment 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

Gene NameMUTYH (mutY homolog (E. coli))
Alias MYH MYHbeta MutYhomolog (hMYH) MutY (E.Coli) homolog mutY homolog
Location 1p34.1
Note MUTYH glycosylase
Description MUTYH is a DNA glycosylase that plays a key role in BER-mediated removal of 8-oxoG:A mismatches.
Note 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).


Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors.
Al-Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, Hodges AK, Davies DR, David SS, Sampson JR, Cheadle JP
Nature genetics. 2002 ; 30 (2) : 227-232.
PMID 11818965
MUTYH-associated polyposis: 70 of 71 patients with biallelic mutations present with an attenuated or atypical phenotype.
Aretz S, Uhlhaas S, Goergens H, Siberg K, Vogel M, Pagenstecher C, Mangold E, Caspari R, Propping P, Friedl W
International journal of cancer. Journal international du cancer. 2006 ; 119 (4) : 807-814.
PMID 16557584
A kindred with MYH-associated polyposis and pilomatricomas.
Baglioni S, Melean G, Gensini F, Santucci M, Scatizzi M, Papi L, Genuardi M
American journal of medical genetics. Part A. 2005 ; 134 (2) : 212-214.
PMID 15690400
Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk.
Croitoru ME, Cleary SP, Di Nicola N, Manno M, Selander T, Aronson M, Redston M, Cotterchio M, Knight J, Gryfe R, Gallinger S
Journal of the National Cancer Institute. 2004 ; 96 (21) : 1631-1634.
PMID 15523092
Proportion and phenotype of MYH-associated colorectal neoplasia in a population-based series of Finnish colorectal cancer patients.
Enholm S, Hienonen T, Suomalainen A, Lipton L, Tomlinson I, Kärjä V, Eskelinen M, Mecklin JP, Karhu A, Järvinen HJ, Aaltonen LA
The American journal of pathology. 2003 ; 163 (3) : 827-832.
PMID 12937124
Germline susceptibility to colorectal cancer due to base-excision repair gene defects.
Farrington SM, Tenesa A, Barnetson R, Wiltshire A, Prendergast J, Porteous M, Campbell H, Dunlop MG
American journal of human genetics. 2005 ; 77 (1) : 112-119.
PMID 15931596
Comprehensive analysis of the contribution of germline MYH variation to early-onset colorectal cancer.
Fleischmann C, Peto J, Cheadle J, Shah B, Sampson J, Houlston RS
International journal of cancer. Journal international du cancer. 2004 ; 109 (4) : 554-558.
PMID 14991577
Prevalence of the Y165C, G382D and 1395delGGA germline mutations of the MYH gene in Italian patients with adenomatous polyposis coli and colorectal adenomas.
Gismondi V, Meta M, Bonelli L, Radice P, Sala P, Bertario L, Viel A, Fornasarig M, Arrigoni A, Gentile M, Ponz de Leon M, Anselmi L, Mareni C, Bruzzi P, Varesco L
International journal of cancer. Journal international du cancer. 2004 ; 109 (5) : 680-684.
PMID 14999774
Germline mutations but not somatic changes at the MYH locus contribute to the pathogenesis of unselected colorectal cancers.
Halford SE, Rowan AJ, Lipton L, Sieber OM, Pack K, Thomas HJ, Hodgson SV, Bodmer WF, Tomlinson IP
The American journal of pathology. 2003 ; 162 (5) : 1545-1548.
PMID 12707038
Mutation analysis of the MYH gene in an Australian series of colorectal polyposis patients with or without germline APC mutations.
Kairupan CF, Meldrum CJ, Crooks R, Milward EA, Spigelman AD, Burgess B, Groombridge C, Kirk J, Tucker K, Ward R, Williams R, Scott RJ
International journal of cancer. Journal international du cancer. 2005 ; 116 (1) : 73-77.
PMID 15761860
Is prophylactic colectomy indicated in patients with MYH-associated polyposis?
Leite JS, Isidro G, Martins M, Regateiro F, Albuquerque O, Amaro P, Romãozinho JM, Boavida G, Castro-Sousa F
Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2005 ; 7 (4) : 327-331.
PMID 15932553
Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway.
Lipton L, Halford SE, Johnson V, Novelli MR, Jones A, Cummings C, Barclay E, Sieber O, Sadat A, Bisgaard ML, Hodgson SV, Aaltonen LA, Thomas HJ, Tomlinson IP
Cancer research. 2003 ; 63 (22) : 7595-7599.
PMID 14633673
Multiplicity in polyp count and extracolonic manifestations in 40 Dutch patients with MYH associated polyposis coli (MAP).
Nielsen M, Franken PF, Reinards TH, Weiss MM, Wagner A, van der Klift H, Kloosterman S, Houwing-Duistermaat JJ, Aalfs CM, Ausems MG, Bröcker-Vriends AH, Gomez Garcia EB, Hoogerbrugge N, Menko FH, Sijmons RH, Verhoef S, Kuipers EJ, Morreau H, Breuning MH, Tops CM, Wijnen JT, Vasen HF, Fodde R, Hes FJ
Journal of medical genetics. 2005 ; 42 (9) : page e54.
PMID 16140997
Attenuated familial adenomatous polyposis and Muir-Torre syndrome linked to compound biallelic constitutional MYH gene mutations.
Ponti G, Ponz de Leon M, Maffei S, Pedroni M, Losi L, Di Gregorio C, Gismondi V, Scarselli A, Benatti P, Roncari B, Seidenari S, Pellacani G, Varotti C, Prete E, Varesco L, Roncucci L
Clinical genetics. 2005 ; 68 (5) : 442-447.
PMID 16207212
MutYH (MYH) and colorectal cancer.
Sampson JR, Jones S, Dolwani S, Cheadle JP
Biochemical Society transactions. 2005 ; 33 (Pt 4) : 679-683.
PMID 16042573
Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH.
Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard ML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP
The New England journal of medicine. 2003 ; 348 (9) : 791-799.
PMID 12606733
A comparison of the phenotype and genotype in adenomatous polyposis patients with and without a family history.
Truta B, Allen BA, Conrad PG, Weinberg V, Miller GA, Pomponio R, Lipton LR, Guerra G, Tomlinson IP, Sleisenger MH, Kim YS, Terdiman JP
Familial cancer. 2005 ; 4 (2) : 127-133.
PMID 15951963
High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis.
Venesio T, Molatore S, Cattaneo F, Arrigoni A, Risio M, Ranzani GN
Gastroenterology. 2004 ; 126 (7) : 1681-1685.
PMID 15188161
MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps.
Wang L, Baudhuin LM, Boardman LA, Steenblock KJ, Petersen GM, Halling KC, French AJ, Johnson RA, Burgart LJ, Rabe K, Lindor NM, Thibodeau SN
Gastroenterology. 2004 ; 127 (1) : 9-16.
PMID 15236166
Germline mutations in the MYH gene in Swedish familial and sporadic colorectal cancer.
Zhou XL, Djureinovic T, Werelius B, Lindmark G, Sun XF, Swedish Low-Risk Colorectal Cancer Group, Lindblom A
Genetic testing. 2005 ; 9 (2) : 147-151.
PMID 15943555


This paper should be referenced as such :
Toschi, B ; Genuardi, M
MAP (MUTYH-Associated Polyposis )
Atlas Genet Cytogenet Oncol Haematol. 2006;10(4):300-301.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]


External links

OrphanetMUTYH-related attenuated familial adenomatous polyposis
Other database/diseases/10805/myh-associated-polyposis MYH-associated polyposis (GARD)
Genes implicated inMUTYH   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  

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