MUTYH-associated polyposis (MAP) is an autosomal recessive colorectal adenomatous polyposis caused by biallelic germline variants in MUTYH, the human homolog of bacterial mutY, which encodes the adenine DNA glycosylase of the base-excision-repair pathway. It is the exception that clarifies the rule among the polyposis syndromes, and its mechanism is deliberately NOT the Knudson two-hit route. MAP carriers inherit two damaged alleles of a repair gene rather than one damaged allele of a tumor suppressor; the resulting defect is a constitutional mutator phenotype rather than a constitutional loss of growth restraint. MUTYH excises adenine that DNA polymerase has misincorporated opposite 8-oxoguanine, the commonest oxidative base lesion. Without it, those mispairs are fixed as G:C to T:A transversions, and the tumor suppressor that actually initiates the adenoma — APC — is then inactivated somatically by exactly that mutational signature. The evidence for this chain is unusually direct: MUTYH was identified by noticing that a family with multiple colorectal adenomas but no germline APC mutation had tumors whose somatic APC mutations were overwhelmingly G:C to T:A transversions, and in confirmed biallelic carriers every somatic APC mutation found was of that type. Clinically MAP presents as multiple (typically 15 to a few hundred) colorectal adenomas, overlapping both attenuated and classic familial adenomatous polyposis, and its recognition matters because the recessive inheritance changes who in the family is at risk: siblings, not offspring, are the high-risk relatives.
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name: MUTYH-Associated Polyposis
creation_date: "2026-08-23T00:00:00Z"
category: Mendelian
categories:
- Hereditary Cancer Syndrome
- Cancer Predisposition Syndrome
- Gastrointestinal Neoplasia
parents:
- hereditary cancer-predisposing syndrome
disease_term:
preferred_term: familial adenomatous polyposis 2
term:
id: MONDO:0012041
label: familial adenomatous polyposis 2
synonyms:
- MAP
- MUTYH-associated polyposis
- MYH-associated polyposis
- autosomal recessive colorectal adenomatous polyposis
description: >-
MUTYH-associated polyposis (MAP) is an autosomal recessive colorectal
adenomatous polyposis caused by biallelic germline variants in MUTYH, the human
homolog of bacterial mutY, which encodes the adenine DNA glycosylase of the
base-excision-repair pathway. It is the exception that clarifies the rule among
the polyposis syndromes, and its mechanism is deliberately NOT the Knudson
two-hit route. MAP carriers inherit two damaged alleles of a repair gene rather
than one damaged allele of a tumor suppressor; the resulting defect is a
constitutional mutator phenotype rather than a constitutional loss of growth
restraint. MUTYH excises adenine that DNA polymerase has misincorporated
opposite 8-oxoguanine, the commonest oxidative base lesion. Without it, those
mispairs are fixed as G:C to T:A transversions, and the tumor suppressor that
actually initiates the adenoma — APC — is then inactivated somatically by
exactly that mutational signature. The evidence for this chain is unusually
direct: MUTYH was identified by noticing that a family with multiple colorectal
adenomas but no germline APC mutation had tumors whose somatic APC mutations
were overwhelmingly G:C to T:A transversions, and in confirmed biallelic
carriers every somatic APC mutation found was of that type.
Clinically MAP presents as multiple (typically 15 to a few hundred) colorectal
adenomas, overlapping both attenuated and classic familial adenomatous
polyposis, and its recognition matters because the recessive inheritance
changes who in the family is at risk: siblings, not offspring, are the
high-risk relatives.
inheritance:
- name: Autosomal recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
penetrance: INCOMPLETE
expressivity: VARIABLE
description: >-
MAP is inherited as an autosomal recessive trait; both MUTYH alleles must be
damaged. This is the single most important practical difference from
APC-related familial adenomatous polyposis, because it relocates the genetic
risk in a family from the offspring of an affected person to their siblings,
and because a family history may appear negative across generations.
evidence:
- reference: PMID:12606733
reference_title: "Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Germ-line MYH mutations predispose persons to a recessive phenotype,
multiple adenomas, or polyposis coli.
explanation: >-
States the recessive inheritance and the range of colorectal phenotypes it
produces.
- reference: PMID:23035301
reference_title: "MUTYH Polyposis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
At conception, each sib of an affected individual has a 25% chance of
being affected, a 50% chance of being a carrier with a small increased
risk for CRC, and a 25% chance of being unaffected and not a carrier.
explanation: >-
GeneReviews Genetic Counseling section, and the quantitative basis for
this entry's claim that siblings rather than offspring are the high-risk
relatives. Note the monoallelic-risk clause in this quote is contested by
the case-control evidence below and is NOT curated here as established.
Evidence source is OTHER because GeneReviews is an expert-authored review.
- reference: PMID:34981295
reference_title: "Monoallelic MUTYH pathogenic variants ascertained via multi-gene hereditary cancer panels are not associated with colorectal, endometrial, or breast cancer."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Using the largest colorectal and endometrial cancer cohorts and one of the
largest breast cancer cohorts from a single case-control study, we did not
observe a significant difference in the prevalence of monoallelic MUTYH
PVs in these cohorts compared to controls.
explanation: >-
PARTIAL rather than SUPPORT or REFUTE, because it cuts both ways against
the item above. It strengthens the recessive architecture this block
asserts — heterozygotes look like the general population — while
contradicting that quote's clause about a small increased colorectal
cancer risk in carriers. Scope limits that keep this from being decisive:
individuals of European ancestry only, and panel-tested cases against
gnomAD controls rather than a population cohort.
- reference: PMID:34981295
reference_title: "Monoallelic MUTYH pathogenic variants ascertained via multi-gene hereditary cancer panels are not associated with colorectal, endometrial, or breast cancer."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
These findings suggest there is no association between colorectal,
endometrial, or breast cancer and MUTYH heterozygosity in individuals of
European ancestry.
explanation: >-
The authors' own conclusion, quoted with its ancestry restriction intact.
Curators should not generalise it beyond European ancestry, and should not
read it as bearing on BIALLELIC carriers, who are the subject of this
entry.
pathophysiology:
- name: Biallelic Germline MUTYH Base-Excision-Repair Deficiency
conforms_to: "genome_instability_mutation#Genome-Maintenance Defect or Replication Stress"
description: >-
Both MUTYH alleles carry damaging germline variants. The two commonest
founder alleles in European populations, Tyr165Cys and Gly382Asp, alter
residues conserved in bacterial mutY — Tyr82, in the
pseudo-helix-hairpin-helix motif predicted to determine mismatch specificity, and Gly253 — and
the corresponding mutant proteins show significantly reduced adenine
glycosylase activity against 8-oxoG:A and G:A substrates. Note this is a
constitutional biallelic state present in every cell, not a first hit
awaiting a second: MAP does not conform to the germline two-hit
predisposition module.
role: trigger
biological_scale: MOLECULAR
gene:
preferred_term: MUTYH
modifier: DECREASED
term:
id: hgnc:7527
label: MUTYH
genetic_context:
gene:
preferred_term: MUTYH
term:
id: hgnc:7527
label: MUTYH
variant_origin: GERMLINE
allelic_hit_role: BIALLELIC_INACTIVATION
allelic_events:
- MISSENSE_VARIANT
- PATHOGENIC_VARIANT
zygosity: COMPOUND_HETEROZYGOUS
functional_impact_category: LOSS_OF_FUNCTION
description: >-
Constitutional biallelic MUTYH variants — homozygous or compound
heterozygous, missense or protein-truncating — reducing adenine glycosylase
activity.
molecular_functions:
- preferred_term: adenine DNA glycosylase activity
term:
id: GO:0019104
label: DNA N-glycosylase activity
modifier: DECREASED
evidence:
- reference: PMID:11818965
reference_title: "Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Analysis of the human homolog of mutY, MYH, showed that the siblings were
compound heterozygotes for the nonconservative missense variants Tyr165Cys
and Gly382Asp.
explanation: >-
Identifies the biallelic germline genotype in the family that defined the
syndrome.
- reference: PMID:11818965
reference_title: "Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Assays of adenine glycosylase activity of the Tyr82Cys and Gly253Asp
mutant proteins with 8-oxoG:A and G:A substrates show that their activity
is reduced significantly.
explanation: >-
Functional evidence that the founder alleles impair the enzyme's catalytic
activity, establishing the repair deficiency at the protein level.
Evidence source is IN_VITRO (biochemical glycosylase assays).
downstream:
- target: Unrepaired 8-Oxoguanine Mispairs and G:C to T:A Transversion Mutator Phenotype
description: >-
Without adenine glycosylase activity, adenine misincorporated opposite
8-oxoguanine is not excised and the mispair is fixed at replication.
- name: Unrepaired 8-Oxoguanine Mispairs and G:C to T:A Transversion Mutator Phenotype
conforms_to: "genome_instability_mutation#Mutator Phenotype and Chromosomal Instability"
description: >-
The rate-limiting state: oxidative damage generates 8-oxoguanine, DNA
polymerase misincorporates adenine opposite it, and the uncorrected mispair
is fixed at the next replication as a G:C to T:A transversion. The result is
a constitutional bias in the kind of mutation the cell accumulates rather
than in the overall rate of chromosomal change, which is why MAP tumors carry
a recognizable mutational signature. The parallel with bacteria is exact and
was the reasoning that identified the gene: loss of mutM or mutY in
Escherichia coli produces the same transversion excess.
role: central_effector
biological_scale: MOLECULAR
biological_processes:
- preferred_term: base-excision repair
term:
id: GO:0006284
label: base-excision repair
modifier: DECREASED
evidence:
- reference: PMID:11818965
reference_title: "Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Inherited defects of base excision repair have not been associated with
any human genetic disorder, although mutations of the genes mutM and mutY,
which function in Escherichia coli base excision repair, lead to increased
transversions of G:C to T:A.
explanation: >-
States the bacterial precedent that predicts the transversion signature,
and establishes MAP as the first human disorder of inherited base-excision
repair deficiency.
downstream:
- target: Somatic APC Inactivation by Transversion
description: >-
The transversion bias is applied genome-wide, but its consequence in
colorectal epithelium is inactivation of APC.
- name: Somatic APC Inactivation by Transversion
description: >-
The transversion-biased mutator phenotype inactivates APC somatically in
colorectal epithelial cells, and the mutational signature is what betrays the
mechanism: in the index family 15 of 18 somatic APC mutations across 11
tumors were of this type, a significantly greater proportion than in sporadic
tumors or in APC-related familial adenomatous polyposis, and in confirmed
biallelic carriers all somatic APC mutations found were G:C to T:A
transversions. MAP therefore reaches the same effector lesion as classic FAP
— APC loss and Wnt pathway activation — but by an entirely different route,
with no germline APC involvement at all.
role: effector
biological_scale: MOLECULAR
genetic_context:
gene:
preferred_term: APC
term:
id: hgnc:583
label: APC
variant_origin: SOMATIC
allelic_events:
- PATHOGENIC_VARIANT
functional_impact_category: LOSS_OF_FUNCTION
description: >-
Somatic APC inactivation acquired through the MUTYH-deficient transversion
signature, in a person with no germline APC mutation.
evidence:
- reference: PMID:11818965
reference_title: "Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Our findings link the inherited variants in MYH to the pattern of somatic
APC mutation in family N and implicate defective base excision repair in
predisposition to tumors in humans.
explanation: >-
Establishes the causal link between the inherited repair defect and the
somatic APC mutational pattern, which is the claim this node makes.
- reference: PMID:12606733
reference_title: "Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In the tumors of carriers of biallelic mutations, all somatic APC
mutations were G:C-->T:A transversions.
explanation: >-
Independent confirmation in a larger series that the somatic APC lesion in
biallelic MUTYH carriers carries the predicted signature without exception.
downstream:
- target: Multiple Colorectal Adenomas and Carcinoma Risk
description: >-
APC-inactivated crypts initiate adenomas, which accumulate in numbers
proportional to the constitutional mutation rate.
- name: Multiple Colorectal Adenomas and Carcinoma Risk
description: >-
The clinical output: multiple colorectal adenomas, most often in the tens to
low hundreds, with progression to colorectal carcinoma. The phenotype spans
the attenuated and classic FAP ranges — about a third of patients with more
than 15 adenomas carried biallelic MUTYH variants in the defining series —
but severe polyposis with more than 1000 adenomas was not seen in biallelic
carriers, so extreme polyp burden argues for APC rather than MUTYH.
Extracolonic disease occurs in a minority.
role: consequence
biological_scale: ORGANISM
evidence:
- reference: PMID:12606733
reference_title: "Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In the group with multiple adenomas, about one third of patients with more
than 15 adenomas had biallelic MYH mutations.
explanation: >-
Quantifies the diagnostic yield of MUTYH testing at the polyp-count
threshold that defines the clinical presentation.
- reference: PMID:12606733
reference_title: "Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In the polyposis group, no patient with biallelic MYH mutations had severe
disease (>1000 adenomas), but three had extracolonic disease.
explanation: >-
Supports both the upper bound on polyp burden in MAP and the occurrence of
extracolonic disease in a minority.
phenotypes:
- category: Gastrointestinal
name: Adenomatous Colonic Polyposis
description: >-
Multiple colorectal adenomas, typically 15 to several hundred, spanning the
attenuated and classic polyposis ranges.
phenotype_term:
preferred_term: Adenomatous colonic polyposis
term:
id: HP:0005227
label: Adenomatous colonic polyposis
evidence:
- reference: PMID:12606733
reference_title: "Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Six patients with multiple adenomas and eight patients with polyposis had
biallelic germline MYH variants.
explanation: >-
Documents biallelic MUTYH variants across both the multiple-adenoma and
polyposis presentations.
- reference: PMID:23035301
reference_title: "MUTYH Polyposis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Although typically associated with ten to a few hundred colonic
adenomatous polyps, CRC develops in some individuals in the absence of
polyposis.
explanation: >-
GeneReviews Clinical Characteristics section, giving the polyp-count range
and the important caveat that colorectal cancer can arise with no
polyposis at all — so a normal polyp count does not exclude the diagnosis.
- category: Gastrointestinal
name: Colorectal Carcinoma
description: >-
Colorectal cancer arising through the adenoma-carcinoma sequence in the
setting of a transversion-biased mutator phenotype.
phenotype_term:
preferred_term: Colon cancer
term:
id: HP:0003003
label: Colon cancer
evidence:
- reference: PMID:11818965
reference_title: "Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We have studied family N, which is affected with multiple colorectal
adenomas and carcinoma but lacks an inherited mutation of the adenomatous
polyposis coli gene (APC) that is associated with familial adenomatous
polyposis.
explanation: >-
Establishes carcinoma as part of the phenotype in the index family, and
the absence of germline APC that distinguishes MAP from FAP.
- reference: PMID:23035301
reference_title: "MUTYH Polyposis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
MUTYH polyposis (also referred to as MUTYH-associated polyposis, or MAP)
is characterized by a greatly increased lifetime risk of colorectal cancer
(CRC).
explanation: >-
GeneReviews Clinical Characteristics section, stating colorectal cancer as
the dominant lifetime risk of the syndrome.
- category: Gastrointestinal
name: Duodenal Polyposis
description: >-
Duodenal adenomas are a common extracolonic feature and carry their own
cancer risk, which is why upper endoscopy with side-viewing duodenoscopy is
part of surveillance rather than an optional extra.
phenotype_term:
preferred_term: Duodenal polyposis
term:
id: HP:0004783
label: Duodenal polyposis
evidence:
- reference: PMID:23035301
reference_title: "MUTYH Polyposis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Duodenal adenomas are common, with an increased risk of duodenal cancer.
explanation: >-
GeneReviews Clinical Characteristics section, establishing duodenal
adenomas as a common feature and the basis for upper-tract surveillance.
- category: Neoplastic
name: Extracolonic Malignancy Risk
description: >-
Beyond the gastrointestinal tract, risk is increased for ovarian and bladder
malignancy, with weaker evidence for breast and endometrial cancer. These
are recorded as an increased risk rather than as penetrant features.
phenotype_term:
preferred_term: Neoplasm by anatomical site
term:
id: HP:0011793
label: Neoplasm by anatomical site
evidence:
- reference: PMID:23035301
reference_title: "MUTYH Polyposis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The risk for malignancies of the ovary and bladder is also increased, and
there is some evidence of an increased risk for breast and endometrial
cancer.
explanation: >-
GeneReviews Clinical Characteristics section. The graded wording is
preserved — ovary and bladder are stated as increased, breast and
endometrium only as "some evidence".
genetic:
- name: MUTYH
gene_term:
preferred_term: MUTYH
term:
id: hgnc:7527
label: MUTYH
relationship_type: CAUSATIVE
notes: >-
MUTYH encodes the adenine DNA glycosylase of base-excision repair. Biallelic
germline variants cause MUTYH-associated polyposis; monoallelic carriage
confers at most a modest colorectal cancer risk and is not this disorder.
evidence:
- reference: PMID:12606733
reference_title: "Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
For patients with about 15 or more colorectal adenomas--especially if no
germ-line APC mutation has been identified and the family history is
compatible with recessive inheritance--genetic testing of MYH is indicated
for diagnosis and calculation of the level of risk in relatives.
explanation: >-
Defines the clinical criteria for MUTYH testing derived from the causal
relationship between biallelic variants and the phenotype.
treatments:
- name: Colonoscopic Surveillance and Polypectomy
notes: >-
Curated under `treatments:` as a management intervention, not as a claim
that endoscopy is itself therapeutic. The initiating lesion here is
constitutional and cannot be reversed — in MAP that is biallelic MUTYH
base-excision-repair failure, not a two-hit tumor suppressor architecture
(see the entry-level `notes:` on the boundary with FAP) — so the only
available lever is stage at detection: surveillance is the intervention
that converts an otherwise unavoidable carcinoma into a resectable polyp.
Where a `target_mechanisms` link is present it points at the
clinical-outcome node for that reason, and never at an upstream
mechanistic node.
description: >-
Because MAP reaches carcinoma through the same adenoma-carcinoma sequence as
the APC-related polyposes, the clinical care of biallelic MUTYH carriers is
the same as for classic or attenuated familial adenomatous polyposis:
endoscopic surveillance with polypectomy, escalating to colectomy when polyp
burden becomes unmanageable.
therapeutic_modality: DEVICE
treatment_term:
preferred_term: Therapeutic Procedure
term:
id: NCIT:C49236
label: Therapeutic Procedure
target_mechanisms:
- target: Multiple Colorectal Adenomas and Carcinoma Risk
treatment_effect: INHIBITS
description: >-
Surveillance and polypectomy do not correct the constitutional repair
defect or the mutator phenotype; they remove initiated adenomas before
they progress, acting on the consequence node.
evidence:
- reference: PMID:12606733
reference_title: "Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Clinical care of patients with biallelic MYH mutations should be similar
to that of patients with classic or attenuated familial adenomatous
polyposis.
explanation: >-
The source's own recommendation that management follow the FAP model,
which is what this treatment entry curates.
- reference: PMID:23035301
reference_title: "MUTYH Polyposis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Colonoscopy with polypectomy every one to two years beginning at age 25-30
years; upper endoscopy and side viewing duodenoscopy every three months to
four years beginning at age 30-35 years with subsequent follow up based on
initial findings.
explanation: >-
GeneReviews Management section, giving the concrete surveillance intervals
and starting ages for both the colonic and duodenal arms.
- name: Colectomy for Unmanageable Polyp Burden
description: >-
Polypectomy is continued until the size and density of polyps outstrip what
endoscopy can manage, at which point subtotal colectomy or proctocolectomy
is performed. The threshold is operational rather than a fixed polyp count.
therapeutic_modality: SURGERY
treatment_term:
preferred_term: Surgical Procedure
term:
id: NCIT:C15329
label: Surgical Procedure
target_mechanisms:
- target: Multiple Colorectal Adenomas and Carcinoma Risk
treatment_effect: INHIBITS
description: >-
Colectomy removes the at-risk colonic epithelium once endoscopic clearance
is no longer feasible; it does not correct the constitutional repair
defect, so duodenal surveillance continues afterwards.
evidence:
- reference: PMID:23035301
reference_title: "MUTYH Polyposis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Suspicious polyps identified on colonoscopy should be removed until
polypectomy alone cannot manage the large size and density of the polyps,
at which point either subtotal colectomy or proctocolectomy is performed.
explanation: >-
GeneReviews Management section, stating both the escalation trigger and
the two operations, which is what this treatment entry curates.
diagnosis:
- name: Molecular Genetic Testing for Biallelic MUTYH Variants
description: >-
The diagnosis requires demonstrating pathogenic variants in BOTH MUTYH
alleles. This is the point at which MAP separates operationally from the
dominant polyposis syndromes: a single variant does not establish the
diagnosis, and the testing question in a polyposis patient with no germline
APC variant and a recessive-compatible family history is specifically
whether both MUTYH alleles are affected.
diagnosis_term:
preferred_term: Genetic Testing
term:
id: NCIT:C15709
label: Genetic Testing
results: >-
Identification of biallelic germline pathogenic MUTYH variants establishes
the diagnosis and makes sibling testing the priority for the family.
evidence:
- reference: PMID:23035301
reference_title: "MUTYH Polyposis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The diagnosis is established in a proband by identification of biallelic
germline pathogenic variants in MUTYH on molecular genetic testing.
explanation: >-
GeneReviews Diagnosis/Testing section, stating the confirmatory test and
the biallelic requirement that defines this disorder.
- reference: PMID:12606733
reference_title: "Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
For patients with about 15 or more colorectal adenomas--especially if no
germ-line APC mutation has been identified and the family history is
compatible with recessive inheritance--genetic testing of MYH is indicated
for diagnosis and calculation of the level of risk in relatives.
explanation: >-
Gives the clinical threshold at which MUTYH testing is indicated, which is
the selection criterion for the test curated here.
references:
- reference: PMID:23035301
title: "MUTYH Polyposis."
tags:
- GeneReviews
prevalence:
- population: Individuals of European ancestry
measure_type: CARRIER_FREQUENCY
prevalence_class: ABOVE_1_IN_1000
rate_per_100000: 1500.0
rate_low: 1000.0
rate_high: 2000.0
notes: >-
Monoallelic MUTYH carrier frequency of 1-2%, normalised to 1000-2000 per
100,000. This is the CARRIER frequency, not the prevalence of
MUTYH-associated polyposis: the disorder is recessive, so affected
individuals are the far rarer biallelic subset. The two must not be
conflated when reading this record.
evidence:
- reference: PMID:34981295
reference_title: "Monoallelic MUTYH pathogenic variants ascertained via multi-gene hereditary cancer panels are not associated with colorectal, endometrial, or breast cancer."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Additionally, frequencies among cancer cohorts were consistent with the
published MUTYH carrier frequency of 1-2%.
explanation: >-
Gives the monoallelic carrier frequency and corroborates it against the
study's own cancer cohorts.
clinical_trials:
- name: NCT07461246
phase: NOT_APPLICABLE
status: ACTIVE_NOT_RECRUITING
description: >-
Italian national multicenter polyposis registry that enrolls
MUTYH-associated polyposis alongside APC-related FAP, collecting the
genotype-phenotype and surveillance-outcome data this entry cites as
absent from single-center series.
target_phenotypes:
- preferred_term: Adenomatous colonic polyposis
term:
id: HP:0005227
label: Adenomatous colonic polyposis
- preferred_term: Colorectal carcinoma
term:
id: HP:0003003
label: Colon cancer
evidence:
- reference: clinicaltrials:NCT07461246
reference_title: Rete Italiana Poliposi Adenomatosa Familiare (RIPAF)
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The registry includes patients with APC-related FAP (classic and attenuated forms), MUTYH-associated polyposis (MAP), and adenomatous polyposis not associated with APC or MUTYH mutations (NAMP)
explanation: >-
Registry record confirming MUTYH-associated polyposis is an enrolled
cohort, so the registry's outcome data will be MAP-specific.
notes: >-
Boundary with familial adenomatous polyposis. MUTYH-associated polyposis and
APC-related FAP are kept as separate entries because they are different
mechanisms that converge on a similar colonic phenotype, not one disease with
two genes. FAP is an autosomal dominant two-hit tumor suppressor syndrome and
conforms to `germline_two_hit_tumor_predisposition`; MAP is autosomal
recessive, requires biallelic MUTYH from the outset, and acts through failed
base excision repair of 8-oxoguanine, so it conforms to
`genome_instability_mutation` instead. The practical consequences differ too:
MAP siblings carry a one-in-four recurrence risk while offspring are usually
unaffected, which is the inverse of the FAP counselling picture. A shared
polyposis registry may enrol both, and this entry cites one that does, but
that is cohort convenience rather than a claim of shared mechanism.