FaCD Online Syndrome Fact Sheet

Last updated: 14 Jan 2010

Co-authors of this topic: Frederik Hes, MD PhD, dept of Clinical Genetics, Leiden University Medical Center, the Netherlands

Name: MUTYH-associated polyposis

Synonym: MAP, MYH-associated polyposis

Mode of Inheritance: AR

OMIM number: 604933  


MUTYH, mapped to 1p32.1-p34.3

Tumor features

colorectal adenomas
colorectal cancer
dudenal adenomas
duodenal cancer
gastrointestinal polyps
ovarian cancer (i.e. epithelial origin)
skin cancer
small intestinal cancer
urinary bladder cancer

Tumor features (possible)

breast cancer
carcinoid, general
colorectal hyperplastic polyps
endometrial cancer
melanoma, cutaneous
sebaceous adenoma
serrated adenomas, colorectal
thyroid cancer, papillary


MAP is characterized by the development of colorectal adenomatous polyps, generally between 10 and 100's, and predisposes for colorectal carcinoma (CRC) in a majority of cases[1-4]. In a series of 107 APC-mutation-negative patients with more than 100 colorectal adenomas (i.e. classic polyposis), 7.5 % had bi-allelic MUTYH mutations. None of these patients with MUTYH mutations had >1000 polyps. All patients with 2 MUTYH mutations had been treated with total colectomy at a mean age of 47.6 years (range 30-70), which is many years older than the average in APC associated FAP (28 years in St Marks series). Some of the patients had duodenal polyps.[3]. Of 152 patients (median age at diagnosis 56 years, range 18-77) with 3 to 100 adenomas, 5 % showed MUTYH mutations and approximately one third of those with >15 adenomas had bi-allelic MUTYH mutations.[3]. Hyperplastic polyps and sessile serrated adenomas have recently been reported as part of MAP[22].

Gastroduodenal polyps and duodenal cancer are part of the MAP phenotype[4,19-20,27]. Multiple jejunal cancer and a desmoid tumor have been observed in a case of aggressive MAP[23]. A Dutch study suggested that breast cancer risk might be increased in MAP patients[4]. Mono-allelic MUTYH mutations are not associated with breast cancer and bi-allelic mutations were not observed in a Canadian series of 691 breast cancer patients[13]. Skin lesions may include pilomatrixomas and sebaceaous gland tumors[15,17,21]. Papillary thyroid cancer[17], endometrial cancer[18,27], chondrosarcoma[20], carcinoid[27], and high-grade astrocytoma[20] has been reported as well[18]. In a recent study, the incidence of extraintestinal malignancies among MAP patients was almost twice that of the general population (SIR 1.9; 95% CI: 1.4-2.5), with a lifetime risk of 38%. Risks to develop ovarian, bladder, and skin cancers were significantly increased (SIR 5.7, SIR 7.2, and SIR 2.8, respectively). A trend of increased risk of breast cancer was also observed. The median ages of onset of these 4 malignancies ranged from 51 to 61 years.[27]

Early-onset colorectal cancer in patients with bi-allelic MUTYH mutations has been diagnosed in the absence of polyposis[5,16]. It has therefore suggested to test patients with early onset colorectal cancer and no tumor signs of deficient mismatch repair for these mutations[16].

Pathological features of the colorectal cancer and tumor immunohistochemistry appear not to be useful in the identification of MAP patients[6]. In contrast, prescreening colorectal cancer for somatic KRAS2 c.34G >T mutations might be useful[14].

One to two percent of the normal population is carrier of one mutated MUTYH allele. Presently, it is unclear if a clinically significant colorectal cancer risk is associated with mono-allelic MUTYH mutations[7-12]. Combined MSH6 and monoallelic MUTYH mutations possibly contribute to colorectal cancer risk[24-26,28].


[1] Al Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, Hodges AK, Davies DR, David SS, Sampson JR, Cheadle JP. Inherited variants of MYH associated with somatic G:C-->A mutations in colorectal tumors. Nat Genet 2002; 30(2):227-232.
[2] Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, Sampson JR, Cheadle JP. Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-->T:A mutations. Hum Mol Genet 2002; 11(23):2961-2967.
[3] Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard ML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP. Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med 2003; 348(9):791-799.
[4] 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. Multiplicity in polyp count and extracolonic manifestations in 40 Dutch patients with MYH associated polyposis coli (MAP). Journal of medical genetics 2005; 42(9):e54.
[5] Wang L, Baudhuin LM, Boardman LA, Steenblock KJ, Petersen GM, Halling KC, French AJ, Johnson RA, Burgart LJ, Rabe K, Lindor NM, Thibodeau SN. MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps. Gastroenterology 2004; 127(1):9-16.
[6] O'Shea AM, Cleary SP, Croitoru MA, Kim H, Berk T, Monga N, Riddell RH, Pollett A, Gallinger S. Pathological features of colorectal carcinomas in MYH-associated polyposis. Histopathology 2008; epub ahead of print.
[7] Croitoru ME, Cleary SP, Di Nicola N, Manno M, Selander T, Aronson M, Redston M, Cotterchio M, Knight J, Gryfe R, Gallinger S. Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk. Journal of the National Cancer Institute 2004; 96(21):1631-4.
[8] Balaguer F, Castellví-Bel S, Castells A, Andreu M, Muñoz J, Gisbert JP, Llor X, Jover R, de Cid R, Gonzalo V, Bessa X, Xicola RM, Pons E, Alenda C, Payá A, Piqué JM, . Identification of MYH mutation carriers in colorectal cancer: a multicenter, case-control, population-based study. Clinical gastroenterology and hepatology 2007; 5(3):379-87.
[9] Olschwang S, Blanché H, de Moncuit C, Thomas G. Similar colorectal cancer risk in patients with monoallelic and biallelic mutations in the MYH gene identified in a population with adenomatous polyposis. Genetic testing 2007; 11(3):315-20.
[10] Jenkins MA, Croitoru ME, Monga N, Cleary SP, Cotterchio M, Hopper JL, Gallinger S. Risk of colorectal cancer in monoallelic and biallelic carriers of MYH mutations: a population-based case-family study. Cancer epidemiology, biomarkers & prevention 2006; 15(2):312-4.
[11] Peterlongo P, Mitra N, Chuai S, Kirchhoff T, Palmer C, Huang H, Nafa K, Offit K, Ellis NA. Colorectal cancer risk in individuals with biallelic or monoallelic mutations of MYH. International journal of cancer 2005; 114(3):505-7.
[12] Peterlongo P, Mitra N, Sanchez de Abajo A, de la Hoya M, Bassi C, Bertario L, Radice P, Glogowski E, Nafa K, Caldes T, Offit K, Ellis NA. Increased frequency of disease-causing MYH mutations in colon cancer families. Carcinogenesis 2006; 27(11):2243-9.
[13] Beiner ME, Zhang WW, Zhang S, Gallinger S, Sun P, Narod SA. Mutations of the MYH gene do not substantially contribute to the risk of breast cancer. Breast cancer research and treatment 2008; epub ahead of print.
[14] van Puijenbroek M, Nielsen M, Tops CM, Halfwerk H, Vasen HF, Weiss MM, van Wezel T, Hes FJ, Morreau H. Identification of patients with (atypical) MUTYH-associated polyposis by KRAS2 c.34G > T prescreening followed by MUTYH hotspot analysis in formalin-fixed paraffin-embedded tissue. Clinical cancer research 2008; 14(1):139-42.
[15] Baglioni S, Melean G, Gensini F, Santucci M, Scatizzi M, Papi L, Genuardi M. A kindred with MYH-associated polyposis and pilomatricomas. American journal of medical genetics. Part A 2005; 134A(2):212-4.
[16] Riegert-Johnson DL, Johnson RA, Rabe KG, Wang L, Thomas B, Baudhuin LM, Thibodeau SN, Boardman LA. The value of MUTYH testing in patients with early onset microsatellite stable colorectal cancer referred for hereditary nonpolyposis colon cancer syndrome testing. Genetic testing 2007; 11(4):361-5.
[17] 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. Attenuated familial adenomatous polyposis and Muir-Torre syndrome linked to compound biallelic constitutional MYH gene mutations. Clinical genetics 2005; 68(5):442-7.
[18] Barnetson RA, Devlin L, Miller J, Farrington SM, Slater S, Drake AC, Campbell H, Dunlop MG, Porteous ME. Germline mutation prevalence in the base excision repair gene, MYH, in patients with endometrial cancer. Clinical genetics 2007; 72(6):551-5.
[19] Nielsen M, Poley JW, Verhoef S, van Puijenbroek M, Weiss MM, Burger GT, Dommering CJ, Vasen HF, Kuipers EJ, Wagner A, Morreau H, Hes FJ. Duodenal carcinoma in MUTYH-associated polyposis. Journal of clinical pathology 2006; 59(11):1212-5.
[20] Buecher B, Baert-Desurmont S, Leborgne J, Humeau B, Olschwang S, Frébourg T. Duodenal adenocarcinoma and Mut Y human homologue-associated polyposis. European journal of gastroenterology & hepatology 2008; 20(10):1024-1027.
[21] Ajith Kumar VK, Gold JA, Mallon E, Thomas S, Hodgson SV. Sebaceous adenomas in an MYH associated polyposis patient of Indian (Gujarati) origin. Familial cancer 2008; 7(2):187-9.
[22] Boparai KS, Dekker E, Van Eeden S, Polak MM, Bartelsman JF, Mathus-Vliegen EM, Keller JJ, van Noesel CJ. Hyperplastic polyps and sessile serrated adenomas as a phenotypic expression of MYH-associated polyposis. Gastroenterology. 2008 Dec;135(6):2014-8
[23] de Ferro SM, Suspiro A, Fidalgo P, Lage P, Rodrigues P, Fragoso S, Vitoriano I, Baltazar C, Albuquerque C, Bettencourt A, Leitão CN. Aggressive phenotype of MYH-associated polyposis with jejunal cancer and intra-abdominal desmoid tumor: report of a case. Dis Colon Rectum. 2009 Apr;52(4):742-5
[24] Giráldez MD, Balaguer F, Caldés T, Sanchez-de-Abajo A, Gómez-Fernández N, Ruiz-Ponte C, Muñoz J, Garre P, Gonzalo V, Moreira L, Ocaña T, Clofent J, Carracedo A, Andreu M, Jover R, Llor X, Castells A, Castellví-Bel S; Gastrointestinal Oncology Group of the Spanish Gastroenterological Association. Association of MUTYH and MSH6 germline mutations in colorectal cancer patients. Fam Cancer. 2009 Aug 15. [Epub ahead of print]
[25] Niessen RC, Sijmons RH, Ou J, Olthof SG, Osinga J, Ligtenberg MJ, Hogervorst FB, Weiss MM, Tops CM, Hes FJ, de Bock GH, Buys CH, Kleibeuker JH, Hofstra RM. MUTYH and the mismatch repair system: partners in crime? Hum Genet. 2006 Mar;119(1-2):206-11.
[26] Steinke V, Rahner N, Morak M, Keller G, Schackert HK, Görgens H, Schmiegel W, Royer-Pokora B, Dietmaier W, Kloor M, Engel C, Propping P, Aretz S; German HNPCC Consortium. No association between MUTYH and MSH6 germline mutations in 64 HNPCC patients. Eur J Hum Genet. 2008 May;16(5):587-92.
[27] Vogt S, Jones N, Christian D, Engel C, Nielsen M, Kaufmann A, Steinke V, Vasen HF, Propping P, Sampson JR, Hes FJ, Aretz S. Expanded extracolonic tumor spectrum in MUTYH-associated polyposis. Gastroenterology. 2009 Sep 1. [Epub ahead of print]
[28] Giráldez MD, Balaguer F, Caldés T, Sanchez-de-Abajo A, Gómez-Fernández N, Ruiz-Ponte C, Muñoz J, Garre P, Gonzalo V, Moreira L, Ocaña T, Clofent J, Carracedo A, Andreu M, Jover R, Llor X, Castells A, Castellví-Bel S; Gastrointestinal Oncology Group of the Spanish Gastroenterological Association. Association of MUTYH and MSH6 germline mutations in colorectal cancer patients. Fam Cancer. 2009;8(4):525-31.