Are some people born with a predisposition to cancer? Cancer, the cause of death in 1 in every 6 people, is caused due to a combination of genetic, lifestyle, and environmental factors. While the latter two can be controlled to an extent, we can’t change the genes we are born with. But learning about your genetic profile can help in significantly reducing cancer risk and even preventing it. MUTYH is one such gene associated with cancer risk. It produces an enzyme that repairs DNA damage. Mutation in this gene causes MUTYH associated polyposis, a condition that increases your risk for colon cancer.
Did You Know? Your 23andMe or any ancestry test DNA data includes 700,000 markers, which can be used to learn everything from disease risk and drug sensitivities to nutritional requirements and fitness parameters. Learn more.
What Is MUTYH Associated Polyposis?
MUTYH-associated polyposis (MAP) is a rare genetic condition where a person has numerous tissue growths in their colon and rectum.
These growths are called adenomatous polyps.
People with MAP can develop between 10 to 100 polyps.
Some people with MAP can develop colorectal cancer with or without polyps.
Causes Of MUTYH Associated Polyposis
Mutations in the MUTYH gene cause MAP.
This gene normally plays a kind of ‘quality control’ role in our cells, helping to fix any mistakes that may occur when our DNA is copied during cell division.
However, when there are errors in the MUTYH gene itself, this repair process can falter, allowing damaged DNA to accumulate.
As a result, other genes responsible for regulating cellular growth, such as APC and KRAS genes, are affected.
Symptoms and Characteristics
MAP typically does not show a lot of symptoms.
Patients can sometimes have the following:
- Bloody stool
- Fatigue from excessive blood loss
- Changes in stool
Patients can show other types of growth apart from colorectal growth.
They can have lumps on the thyroid and adrenal glands.
Dental abnormalities such as jawbone cysts are also common for patients having MAP.
Growths inside the eyes called congenital hypertrophy of the retinal pigment epithelium might be present.
Genetics Behind MUTYH Associated Polyposis
Underlying Genes
Mutations in the MUTYH gene cause MAP.
The two most common mutations are Y165C and G382D.
Additional alterations can be found in complete gene sequencing tests.
To have MAP, a person must have two copies of the mutated MUTYH gene.
How Is It Inherited?
MUTYH-associated polyposis is inherited in an autosomal recessive pattern.
It means both parents must be carriers of the disease for it to appear in their children.
The children of two mutation carriers can have three different scenarios:
- There is a 25% chance that the children will neither be carriers of this disease nor suffer from it.
- There is a 50% chance of being a carrier. These people will not suffer from MAP but can pass on the mutation to their children.
- Then there is a 25% chance that the person will inherit the gene mutation and suffer from MAP.
What Is The Risk Of Being A MUTYH Carrier?
Studies show that 1 in every 100 people carries a mutation in the MUTYH gene.
You run the risk of being a carrier if either of your parents had the MUTYH gene mutation.
It indicates that you will not suffer from MAP but can pass on the disease to your children.
You will likely suffer from this disease if your parents have a MUTYH gene mutation.
Is MUTYH-associated polyposis a cancer risk?
People with MAP are at an increased risk of developing colon and rectal cancer.
Almost half of all people with MAP will have colorectal cancer at diagnosis.
Those with a single MUTYH gene mutation have a higher chance of developing cancer.
Most colorectal cancers occur between 40 to 60 years of age.
Are Other Types of Cancers Associated With This Condition?
MAP increases the chances of thyroid and duodenal cancer.
The gene mutation associated with MAP affects all the cells of the body.
Patients with MAP run the risk of developing stomach polyps and duodenal adenoma.
Chances of breast and ovarian cancer are also increased in women suffering from MAP.
Diagnosis and Screening Measures
Genetic testing is required to diagnose MAP.
Your symptoms and family history will also help determine whether you suffer from MAP.
You have an increased risk of MAP if
- You are younger than 60 years and have ten or more colorectal adenomas.
- You have more than 20 adenomas at any age.
- You have duodenal polyps or cancer.
Patients diagnosed with MAP should undergo screenings to monitor their condition and rule out possible cancer.
The screenings suggested by doctors are:
- Annual physical exam
- Routine colonoscopies every one to two years from 25 years of age.
- Regular endoscopy and duodenoscopy from 35 years of age.
- Thyroid ultrasound
- Regular skin cancer screenings
Genetic Testing For MUTYH Associated Polyposis
MAP genetic testing helps doctors see if you have changes or mutations in your MUTYH gene.
Anyone can do this test, but it’s especially useful if you or your family have had many colon polyps or colon cancer.
A doctor or genetic counselor will guide you on how to do this, often through a simple blood test.
If you test positive, it means you have a mutation.
It doesn’t mean you have or will get cancer, but you’re at higher risk. Doctors will guide you on what to do, like getting more regular colon checks.
If you test negative, it means you don’t have the mutation.
But it doesn’t mean you won’t ever get colon polyps or cancer, so you should still follow your doctor’s advice for routine checkups.
Remember, this test is just a tool. It’s a way to understand your risk so you and your doctors can make the best health decisions.
Management and Treatment
MAP cannot be cured.
Treatment focuses on preventing cancer and maintaining a healthy lifestyle for patients.
Patients are advised to undergo regular colonoscopy to monitor their condition.
If there are less than 20 polyps, they can be removed by a polypectomy procedure during colonoscopy.
If the polyps are numerous and growing fast, then surgical removal of the colon or rectum may be necessary.
This procedure is called colectomy.
Laparoscopic surgery has made colectomy a less painful and disabling procedure.
Surgical intervention might be the last resort to prevent cancer.
Some non-steroidal, anti-inflammatory drugs, such as sulindac, can reduce and prevent the growth of polyps.
Thyroid ultrasound and genetic testing are also recommended for MAP patients.
Summary
MUTYH Associated Polyposis (MAP) is a rare genetic condition with abnormal growths on the colon and rectum, called polyps.
This condition makes the patient prone to develop colorectal cancer.
It also increases the chances of thyroid, breast, and ovarian cancers.
MAP can be diagnosed by genetic testing.
This condition does not have a cure.
Treatment includes surgically removing the polyps or laparoscopic surgery to remove the colon or rectum.
Patients should be regularly monitored to rule out possible signs of cancer.
References
https://my.clevelandclinic.org/health/diseases/17254-myh-associated-polyposis
https://rarediseases.info.nih.gov/diseases/10805/myh-associated-polyposis
https://www.ncbi.nlm.nih.gov/books/NBK107219/
https://www.nature.com/articles/s41467-022-30916-1
https://www.cancer.org/cancer/types/colon-rectal-cancer/about/what-is-colorectal-cancer.html
