MUTYH Associated Polyposis (MAP)
Pp. 66-100 (35)
M.L.M. Binderup and M.L. Bisgaard
MUTYH Associated Polyposis (MAP) is an autosomal recessive predisposition
to polyposis and colorectal cancer (CRC) caused by biallelic mutations in the base excision
repair (BER) gene MUTYH. Phenotypically, MAP is difficult to distinguish from other
hereditary CRC syndromes like Familial Adenomatous Polyposis (FAP) and to a lesser
extent Hereditary Non-Polyposis Colorectal Cancer (HNPCC), known to be caused by
germline mutations in the APC and Mismatch Repair (MMR) genes, respectively. Here we
review the main genetic and clinical aspects of MAP and aim to provide a broad, up-to-date
overview of existing findings regarding MAP.
The exact role of MUTYH in CRC tumorgenesis is not fully determined, but a defective BER
system due to germline MUTYH mutations leads to somatic mutations in the APC gene.
Furthermore, cooperation between the BER and MMR systems exists, and possibly
monoallelic defects in both pathways are of significance to CRC development. The two most
common MUTYH variants, Y179C and G396D, both generate dysfunctional gene products,
but Y179C has the most severe functional consequences and possibly causes a more severe
Median clinical onset of MAP is 47 years of age, and due to the recessive mode of inheritance,
most have already developed CRC. Typically MAP patients develop between 10-100
colorectal adenomas, although polyposis may not be obligatory for MAP. Typical FAP and
HNPCC associated extracolonic manifestations are not common in MAP, except for upper
gastro-duodenal polyposis which can be part of the phenotype, but more seldom than in FAP.
Recommended MAP surveillance is colonoscopy with polypectomy from 20-25 years of age.
In the future, genetic testing as well as surveillance may be targeted according to specific ethnic
MUTYH mutation variants and genotype-phenotype correlations.
Colorectal Cancer, MUTYH Associated Polyposis, The MUTYH gene,
Base excision repair, (Attenuated) Familial Adenomatous Polyposis, Hereditary
Non-Polyposis Colorectal Cancer.
Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute 24.4, Blegdamsvej 3, 2200 Copenhagen N, Denmark