MUTYH-associated polyposis

(MAP)
 Questions & Answers by James Park


    Hello relatives and fellow patients,

    I have MUTYH-associated polyposis (MAP),
an inherited genetic defect
that gives rise to polyps (pre-cancerous growths)
on the inside of my colon (large intestine).

    This Internet portal is one patient's attempt
to understand and explain this rare medical problem.
Other patients might want to do more research on our syndrome,
but here I hope to present the basic facts
in terms that can be understood by anyone,
since most of us do not need to delve too deeply into the technical details.



1.  WHAT IS MUTYH-ASSOCIATED POLYPOSIS?

    This inherited defect in our DNA is named after the specific gene
where the mis-coding is found—the MUTYH gene.

    (This gene is located on the short arm of chromosome 1—called 1p.)

    In my case, I have the genetic defects called: Y165C and C382D.
These are some of the more common DNA errors
that cause MUTYH-associated polyposis.
Other defects have been identified, especially in non-Europeans.

    This syndrome used to be called MYH-associated polyposis.
This change of name came about because the gene was re-named.

    Perhaps about 1% of all colorectal cancers
are caused by MUTYH-associated polyposis.


2.  HOW ARE SUCH DEFECTS DISCOVERED?

    Because these inherited mistakes in my DNA exist in every cell of my body,
a simple blood test was all that was required to establish these facts.

    My relatives and other patients can also discover whether or not
they have such defects by asking for blood tests that look at the MUTYH gene.



3.  WHERE DO SUCH DEFECTS OF DNA COME FROM?

    Such errors in the DNA 'spelling' have been present since our species emerged.
About 1% of human beings with European roots have one such misspelling.

    And as far as we know,
having just one spelling-error in this part of our DNA causes no problems.
These individuals are carriers of the defect,
which means that they might pass that error on to their children.

    Only if we get TWO defects—one from each parent—
do we develop MUTYH-associated polyposis.
(This is called recessive inheritance.)

    One of my genetic defects came from my mother and one from my father.
Neither of them had polyps or the colon cancer that can follow.
(But my mother did die at an early age from breast cancer,
which might have been related in some way to her defect.)

    Parents are in no way responsible for 'their' genes.
They did nothing to choose these genetic defects.
And they could have done nothing
to prevent or eliminate these problems in their DNA.

    Both of my parents have been dead for many years,
so there is no easy way to discover which one had which defect.
And I am the only first generation descendent of these two people
who received both defects when I was conceived.
Other descendants of my two parents
might have one or the other of these defects.

    See more about genetic testing in question 11 below.



4.  HOW COMMON IS MUTYH-ASSOCIATED POLYPOSIS?

    If we were to line up 1,000 hospital beds,
each with one patient with colorectal cancer,
only 3-5 beds would be occupied by patients with MUTYH-associated polyposis.
In other words, these genetic defects explain
less than one-half of one percent of all cancers of the large intestines.
As more patients receive genetic testing,
this number might rise to as many as 10 patients
out of 1,000 with colon cancer (1%).

    The fact that we have such a rare form of cancer in this location
might lead to inappropriate treatment recommendations
from doctors familiar with the more common colon problems.



5.  HOW DOES MUTYH-ASSOCIATED POLYPOSIS MANIFEST ITSELF?

    As the name suggests,
the most common result of having two defects in one's MUTYH gene
is the formation of multiple polyps in one's large intestine or colon,
which forms the bottom end of the digestive tract.

    If not treated by colonoscopy,
at least some of these polyps will turn into cancers.
These colon cancers typically appear about age 50
—as was true in my case. 



6.  WHAT CAUSES THE POLYPS?

    Polyps develop in our colons
because of normal mistakes in the reproduction of cells.
Most such mutations in most people cause no problems.

    One reason that random mutations usually do not lead to cancer
is that most people have a 'spell-checker' to correct mistakes.

    Our DNA is a very long chain of molecules in the form of a double helix.
There are only four different 'letters' in this very long word.
And every time any cell in our bodies divides to reproduce,
it must create a new strand of DNA for that new cell.

    Cleverly, the human body has a method of correcting any mistakes
introduced when the new strand of DNA is copied from the old.

    But patients with MUTYH-associated polyposis lack this repair mechanism.
So for them (us), the spelling errors go uncorrected.
We lack the little engines that go along the zipper
to make certain that everything was perfectly copied.

    And after random changes occur at the microscopic level,
the affected cells continue to reproduce,
creating polyps that can be seen (with a special scope) on the inside of the colon.
These cells are now reproducing without controls.
If not removed by colonoscopy,
some of these bumps will slowly grow in size over the years
until they form cancerous polyps,
which can eventually choke off our digestive tracts,
then finally causing symptoms we can no longer ignore.



7.  WHAT ARE THE CHANCES OF GETTING CANCER? 

    100%---if the polyps are not removed before they become cancerous.

    I and all the other people reading these words who have MUTYH-associated polyposis
have been maturing toward colon cancer
from the moment our parent's gametes united to form our unique DNAs
—that is, from the moment of conception.

    It is no one's fault.
Until the 21st century, it was not yet possible to know who was a carrier
---that is, who had one defect of the MUTYH gene.
And couples who reproduced had no way of knowing
when both the male and the female had these defective genes.

    But if we had the good fortune of discovering our cancers early,
complete cure is possible.
And ever thereafter we will have to be followed
to make sure that no new polyps in our digestive tract become cancerous.

    And even more fortunate would be to have our polyps discovered
before they became cancerous.
Treating pre-cancerous polyps is the only way
to avoid cancer caused by MUTYH-associated polyposis.



8.  HOW QUICKLY DO POLYPS BECOME CANCEROUS?

    Medical research concerning all forms of colon polyps
has now concluded that polyps arising from all causes
develop very slowly toward possibly-harmful cancers.
It might take five years or more from the first visible polyp
to go thru its well-understood stages of development
finally to become a colon cancer that has symptoms.



9.  WHAT ARE THE TREATMENT OPTIONS?

    Precisely because of this very slow development
from polyps to cancer,
it is sometimes possible to manage this syndrome
using regular colonoscopy alone.
As long as all visible polyps are removed or killed,
they will not become dangerous.
About half of MUTYH-patients have been managed in this way.

    The other half have their colons completely removed,
which is a sure-fire way to prevent any future colon cancers.

    Which option is best for you will depend on
the number of cancers you already have in your colon,
how many new polyps you develop each year,
and other factors such as your age and general health.

    Because I am otherwise in excellent health,
I have chosen to keep my colon
and have it inspected once a year to treat the new polyps.
My example should not be taken as a recommendation for others.
Get as much information as possible from your medical providers.
And get second opinions, especially from medical professionals
who have treated MUTYH-associated polyposis before.



10.  HOW IS MUTYH-ASSOCIATED POLYPOSIS
RELATED TO FAMILIAL ADENOMATOUS POLYPOSIS?

    Familial Adenomatous Polyposis (FAP) is a much more common syndrome.
However, as the name suggests, this genetic defect runs in families:
It was first identified by the fact that each generation
had some patients with this form of colorectal cancer.

    My first clue that I did not have FAP when my colon cancer was discovered
was the fact that there are no other members of my family with similar problems:
None of my ancestors about whom I know anything had colon cancer.
And now none of my siblings or their descendants have colon cancer.
(I have no biological descendants of my own.)

    Familial Adenomatous Polyposis (FAP)
comes from a completely different genetic error.
FAP is caused by a variation in the long arm of chromosome 5.
The responsible gene is called APC.
And in this syndrome, the inheritance is dominant (rather than recessive),
meaning that each biological descendant has a 50% change of having FAP.

    The variations of the APC gene that lead to FAP
is found in about 1 person per 10,000 in all populations of human beings.

    FAP manifests itself with sometimes thousands of polyps.
And the universal cure or prevention is to remove the whole colon.
With FAP, if you don't have cancer yet, you will get it later.
So it makes sense to have the surgery as early in your life as possible.

    (And doctors with experience dealing with FAP
might give the same advice to MUTYH-patients,
thinking that they all have the same fate.
But new research shows that this is not so.
We can be sympathetic toward our fellow-patients who have FAP,
but the same treatment might not be required for us.)

    Thus, it will be a relief to have genetic testing show
that our APC gene is not affected
but that our problem with polyps arises from our MUTYH gene.
In my case, genetic testing has shown exactly this fact:
My APC gene is not defective.



11.  SHOULD RELATIVES OF PATIENTS
WITH MUTYH-ASSOCIATED POLYPOSIS
GET GENETIC TESTING?

    Genetic testing for variations in the MUTYH gene
only became available in the first decade of the 21st century.

    What we all want to avoid for future generations
is the creating of new individuals who have the MUTYH-syndrome described here.

    If both parents are carriers—each having one variation of the MUTYH gene—
then there is a 25% chance for each child they reproduce
will get this cancer-causing genetic syndrome. 

    I am very glad that I have had my life, even tho I have this syndrome.
But future prospective parents have the option of being tested
before they decide to have children together.

    And even if a child with this MUTYH double-defect is born,
we now know how best to prevent cancer from developing.

    Will future mate-selection include genetic testing
to see which pairings have a chance of creating
off-spring with MUTYH-associated polyposis?

    The newest genetic testing
can check embryos created outside the mother's body.
The fertility-clinic can take a single cell from each embryo
to see if it has two MUTYH defects.
Embryos that would create human beings with MUTYH-associated polyposis
can be discarded—not implanted in the mother—
and those embryos without any such genetic defects can be implanted. 

    When considering which family members to test for MUTYH defects,
it makes most sense to test the oldest living relative
who has some biological descendants.
If that individual has no defect, none of the descendants will have it.
If the tested MUTYH gene is defective, children, grandchildren, etc.
might also have this same inherited variation.



12.  WHAT OTHER CANCERS SHOULD WE WATCH FOR?

    Because we have a defect in our repair mechanism,
it is quite possible for other cancers to emerge in our bodies.

    Our upper gastrointestinal tract should also be inspected for polyps.
17-30% of MUTYH patients also have duodenal polyposis,
—polyps in the part of the small intestine that leads off the stomach.

    Cancers are also more likely in other parts of our bodies.
In general, our risk of non-intestinal cancers is twice as high as the general population.
Our life-time risk of other cancers is 38%.

    Bladder cancer is 7.2 times as likely as in the general population.

    Skin cancer is 2.8 times as likely.
(I have had basal-cell carcinoma on my nose.)

    Females with two MUTYH variations have breast cancer about 18% of the time.

    Another variation, which I have and which is common for patients with FAP, is
osteomas—hard harmless bony tumors just inside the teeth of my lower jaw.



13.  WHAT WILL BE OUR CAUSE OF DEATH?

    Every person who reads these words will eventually have a listed cause of death.
Our death-certificates might list the primary cause, followed by contributing factors.

    We who have MUTYH-associated polyposis
will probably have cancer listed as our primary cause of death.

    Greater knowledge about this specific syndrome caused by our genetic defect
can protect us from the most common form of cancer-death—colorectal cancer.
And we can take care to watch for the other cancers
known to be associated with our MUTYH variations.

    But there are many parts of our bodies which cannot be seen as readily,
even using all of the scopes now available to our doctors.

    We should do our best to notice anything that might point to a cancer developing.
But our MUTYH defects, which we have had since our conception,
will probably prove to be the genetic cause of our deaths.

    Of course, we might die from any of the other possible causes of death:
heart-and-circulatory problems, organ failure, infection, or accident.
Or we might live long enough to die with several degenerative problems.

    And being explicit with our doctors about any other problems we might have
can help to shape the best responses to the MUTYH-caused problems.


>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

    The information included in this website
was mostly found on the Internet.
Others are invited to do their own searches:
"MUTYH-associated polyposis".

One good resource you will discover is:

http://www.cancer.net/cancer-types/myh-associated-polyposis

This website presents basic information intelligible to laypersons.

And it is updated as new information becomes available.

    If I have misunderstood anything or omitted anything important,
please let me know, so I can improve these questions and answers.
E-mail: parkx032@umn.edu



    Here is one recent book that has a chapter on our syndrome:

Sue Clark, editor

A Guide to Cancer Genetics in Clinical Practice

(Harley, UK: tfm Publishing: www.tfmpublishing.com, 2009)       238 pages
(ISBN: 978-1-903378-54-0; paperback)
(Library of Congress call number: not given in book)
(Medical call number: QZ200G9457 2009)

    14 chapters on various dimensions of the genetic bases of cancer.

Created December 5, 2014; Revised 12-10-2014; 12-16-2014; 12-21-2014; 12-23-2014; 12-30-2014;
1-12-2016; 2-12-2016; 8-2-2017; 2-21-2018; 3-9-2018; 4-10-2019; 


Read a more personal statement here:
MUTYH-ASSOCIATED POLYPOSIS:
A PATIENT'S PERSPECTIVE

KEEPING MY COLON:
25 YEARS AND COUNTING

MRI for MAP
Magnetic Resonance Imaging
for patients with
MUTYH-Associated Polyposis
https://s3.amazonaws.com/aws-website-jamesleonardpark---freelibrary-3puxk/MRI-MAP.html



Go to the beginning of this website
James Leonard Park—Free Library