The MUTYH gene provides fundamental instructions within our bodies, playing an important role in maintaining the integrity of our genetic material. It is crucial for safeguarding our genetic code and ensuring proper cellular function.
Normal Function of the MUTYH Gene
The MUTYH gene provides instructions for creating an enzyme called MYH glycosylase, which is directly involved in DNA repair. This enzyme works to correct specific errors that occur during DNA replication, the process where DNA is copied before cell division.
DNA is composed of building blocks known as nucleotides, which typically pair in a precise manner: adenine with thymine (A-T) and guanine with cytosine (G-C). However, during normal cellular activities, guanine can sometimes be altered by oxygen, leading it to incorrectly pair with adenine instead of cytosine. MYH glycosylase identifies and fixes this particular error, preventing the accumulation of mutations in the DNA that could otherwise lead to uncontrolled cell growth. This specific repair is referred to as base excision repair.
Understanding MUTYH-Associated Polyposis
When both copies of the MUTYH gene have mutations, it impairs the cell’s ability to correct DNA errors, leading to a condition called MUTYH-associated polyposis (MAP). This autosomal recessive disorder results in the accumulation of genetic mistakes within cells, which can cause abnormal tissue growths called polyps, primarily in the colon and rectum. While polyps themselves are not cancerous, they have a high potential to develop into colorectal cancer if not removed.
Individuals with MAP typically develop multiple polyps, ranging from 10 to hundreds. This condition significantly increases the lifetime risk of colorectal cancer, with estimates ranging from 80% to 90% if polyps are not managed through surveillance and removal. Approximately half of all people diagnosed with MAP already have colorectal cancer at the time of their diagnosis, often between the ages of 40 and 60. Beyond colorectal cancer, MAP also raises the risk for other cancers, including duodenal cancer, with a lifetime risk of approximately 4%, and potentially gastric, ovarian, thyroid, bladder, and breast cancers.
Inheritance Patterns and Family Risk
MUTYH-associated polyposis follows an autosomal recessive inheritance pattern, meaning an individual must inherit a mutated copy of the MUTYH gene from both parents to develop the condition. If a person inherits a mutation from only one parent, they are considered a “carrier” and typically do not develop MAP. Carriers can pass the mutated gene on to their children.
If both parents are carriers of a single MUTYH gene mutation, each of their children has a 25% chance of inheriting two mutated copies and developing MAP, a 50% chance of being a carrier, and a 25% chance of inheriting no mutated copies. While carriers generally do not develop MAP, some studies indicate they may have a slightly increased risk of colorectal cancer, particularly if there is a family history of the disease. For individuals with MAP, their children will always inherit at least one mutated MUTYH gene copy, and their risk of developing MAP depends on the genetic status of their other parent.
Screening and Management Strategies
Genetic testing confirms a diagnosis of MUTYH-associated polyposis by identifying biallelic mutations in the MUTYH gene. For individuals diagnosed with MAP, regular surveillance is recommended to manage cancer risk.
This primarily involves high-quality colonoscopies every one to two years, starting between ages 25 and 30, to detect and remove polyps early. Upper endoscopy with a specialized scope is also advised, typically starting between ages 30 and 35, with follow-up frequency determined by polyp findings.
Other potential surveillance measures include annual physical examinations, thyroid ultrasounds, and skin examinations, though specific guidelines for these are less standardized. In cases with a high polyp burden or existing cancer, surgical options like total colectomy may be considered.