Gene guide
MUTYH gene: DNA repair, polyposis and colon cancer
MUTYH is a DNA repair gene that fixes a common type of oxidative damage. Inheriting two faulty copies causes MUTYH-associated polyposis (MAP), with many colon polyps and a high risk of colorectal cancer. Inheriting one copy makes you a carrier, which is common and much lower risk.
- Full name
- mutY DNA glycosylase (formerly MYH)
- Chromosome
- 1 (1p34.1)
- Role
- Base excision repair: removes adenine wrongly paired with 8-oxoguanine, a common product of oxidative DNA damage
- Condition
- MUTYH-associated polyposis (autosomal recessive)
- Common pathogenic variants
- Y179C and G396D (previously called Y165C and G382D) in people of European descent
What does MUTYH do?
Reactive oxygen species constantly damage DNA. One of the most common lesions is 8-oxoguanine, which can mispair with adenine when DNA is copied. If that error isn't fixed, the next round of copying fixes a G:C to T:A change permanently. MUTYH is the enzyme that spots adenine sitting opposite 8-oxoguanine and removes it, so the correct base can be put back. It works with OGG1 and MTH1 in the "GO" repair system.
How MUTYH was linked to polyposis
In 2002, researchers studied a family ("family N") with multiple colorectal adenomas and cancer but no APC mutation, the usual cause of polyposis. Their tumors were full of G:C to T:A changes in the APC gene. The affected siblings carried two different MUTYH variants, Tyr165Cys and Gly382Asp (now numbered Y179C and G396D), which both reduced the enzyme's activity (Al-Tassan 2002).
A larger study the next year confirmed a recessive pattern: about one third of patients with more than 15 adenomas and no APC mutation had two MUTYH variants, and the authors recommended MUTYH testing for people with about 15 or more adenomas (Sieber 2003).
MUTYH-associated polyposis (MAP)
People with two pathogenic MUTYH variants typically develop tens to hundreds of colon polyps, usually from their 40s or 50s, and have a high lifetime risk of colorectal cancer without surveillance. They also have higher risks of duodenal polyps and some other cancers. Because MAP is recessive, parents are usually unaffected carriers and there may be no family history. Regular colonoscopy, with polyps removed, greatly lowers the risk (see the GeneReviews summary below).
Being a MUTYH carrier
About 1 to 2% of people of European descent carry one pathogenic MUTYH variant. Carriers do not get MAP. Their colorectal cancer risk is, at most, slightly higher than average, and many guidelines recommend screening based on family history rather than carrier status alone. Carriers can pass the variant on, so a partner's status matters for children: if both partners are carriers, each child has a 1 in 4 chance of MAP.
Can raw DNA data detect MUTYH variants?
The two most common variants are sometimes on consumer chips, but chip results for rare variants are often wrong. In UK Biobank, only 16% of very rare variants called by SNP chips were confirmed by sequencing (Weedon 2021), and a clinical laboratory found that 40% of variants from consumer raw data sent for confirmation were false positives (Tandy-Connor 2018). Any MUTYH finding should be confirmed with clinical testing, ideally through a genetic counselor. Whole genome sequencing reads the whole gene.
What can you do?
- If you have many polyps (around 10 or more adenomas) or colorectal cancer at a young age, ask about genetic testing for MUTYH and APC.
- If you have MAP, follow a specialist surveillance plan; colonoscopy every one to two years is common.
- If you are a carrier, follow standard or family-history-based colorectal screening, and tell siblings and partners.
- For everyone: not smoking, limiting processed meat and alcohol, staying active and eating fiber lower colorectal cancer risk.
NutraHacker reports that include MUTYH
Every raw DNA upload also gets a free Detoxification and Methylation Report, genome imputation and a Superhuman traits report. See what you can do with raw DNA data.
Related reading
- TP53 and Li-Fraumeni syndrome
- Glossary: autosomal recessive
- Glossary: carrier
- Glossary: compound heterozygous
- Glossary: oxidative stress
Frequently asked questions
What does the MUTYH gene do?
It repairs a common type of oxidative DNA damage by removing adenine mispaired with 8-oxoguanine, preventing G:C to T:A mutations.
What is MUTYH-associated polyposis?
An inherited condition caused by two faulty copies of MUTYH. It leads to many colon polyps and a high risk of colorectal cancer without regular colonoscopy.
I am a MUTYH carrier. Am I at risk of cancer?
Carriers do not get MAP. Their colorectal cancer risk is at most slightly higher than average; screening is usually based on family history. Tell relatives and partners.
How common are MUTYH carriers?
About 1 to 2% of people of European descent carry one pathogenic MUTYH variant, most often Y179C or G396D.
Can 23andMe raw data show a MUTYH mutation?
Some chips include the common variants, but chip results for rare variants are often false positives. Confirm any finding with clinical testing.
References
- Al-Tassan N, et al. Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors. Nat Genet. 2002;30(2):227-32. PubMed 11818965
- Sieber OM, et al. Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med. 2003;348(9):791-9. PubMed 12606733
- MUTYH Polyposis. In: GeneReviews. University of Washington, Seattle; 1993-. PubMed 23035301
- Weedon MN, et al. Use of SNP chips to detect rare pathogenic variants: retrospective, population based diagnostic evaluation. BMJ. 2021;372:n214. PubMed 33589468
- Tandy-Connor S, et al. False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care. Genet Med. 2018;20(12):1515-1521. PubMed 29565420