Kenneth Kee 2017 Smashwords Edition
by Kenneth Kee at Smashwords.com
book is dedicated
my wife Dorothy
book describes Lynch Syndrome, Diagnosis and Treatment and Related
Diseases which is seen in some of my patients in my Family Clinic.
You Need to Treat Lynch Syndrome)
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you for respecting the hard work of this author.
I have been writing
medical articles for my blog http://kennethkee.blogspot.com
(A Simple Guide to Medical Condition) for the benefit of my patients
My purpose in writing
these simple guides was for the health education of my patients.
Health Education was
also my dissertation for my Ph.D (Healthcare Administration).
I then wrote an
autobiolographical account of his journey as a medical student to
family doctor on his other blog
account “A Family Doctor’s Tale” was combined with my early “A
Simple Guide to Medical Conditions” into a new Wordpress Blog “A
Family Doctor’s Tale” on http://kenkee481.wordpress.com.
From which many free
articles from the blog was taken and put together into 800 amazon
kindle books and 200 into Smashwords.com eBooks.
Some people have
complained that the simple guides are too simple.
For their information
they are made simple in order to educate the patients.
The later books go into
more details of medical conditions.
The first chapter is
always from my earlier blogs which unfortunately tends to have typos
and spelling mistakes.
Since 2013, I have
tried to improve my spelling and writing.
As I tried to bring you
the latest information about a condition or illness by reading the
latest journals both online and offline, I find that I am learning
more and improving on my own medical knowledge in diagnosis and
treatment for my patients.
Just by writing all
these simple guides I find that I have learned a lot from your
reviews (good or bad), criticism and advice.
I am sorry for the
repetitions in these simple guides as the second chapters onwards
have new information as compared to my first chapter taken from my
I also find repetition
definitely help me and maybe some readers to remember the facts in
the books more easily.
I apologize if these
repetitions are irritating to some readers.
What is Lynch syndrome?
Lynch syndrome is an
inherited medical disorder that confers a person a higher risk of
cancers of the digestive tract, gynecologic tract, and other organs.
In Singapore Lynch
syndrome has an estimated incidence of 1 in 300 in women and 1 in 500
in the general population.
People who have Lynch
syndrome have a considerably higher danger of forming:
1. Colorectal cancer
3. Gastric (stomach)
4. Ovarian cancer,
5. Small bowel (small
6. Pancreatic cancer,
7. Urinary tract cancer
(bladder or ureter cancer),
8. Kidney cancer,
9. Bile duct cancer,
10. Certain skin tumors
(sebaceous tumors of the skin or sebaceous adenomas), and
11. Brain tumors.
People with Lynch
syndrome may also be at slightly higher risk of:
1. Breast cancer and
2. Prostate cancer.
The old term for Lynch
syndrome was “hereditary non-polyposis colorectal cancer”
There is no likelihood
toward polyp formation and hence the name HNPCC.
It is the most frequent
genetic syndrome linked with a higher vulnerability to Colon cancer.
Typical Features of
Patients with Lynch
syndrome have a 60%-80% risk for Colorectal Cancer (CRC), as well as
a higher risk for cancers, most conspicuously endometrial cancer
Endometrial cancer is
the second most frequent malignancy in Lynch syndrome with a lifetime
danger between 40% and 60%, often happening before Colorectal Cancer
(CRC) in females.
Lynch syndrome is also
linked with a higher relative danger for cancer in the stomach,
ovary, small bowel, pancreas, ureter, renal pelvis, biliary tract,
One of the major
features (phenotype) of Lynch syndrome carriers is that cancer often
forms at an earlier age than in the normal population
The average age of
start for colorectal cancer and endometrial cancer for patients with
Lynch syndrome is about 44 and 48 years, respectively, compared to 65
years for colorectal and 60 years for endometrial sporadic carcinomas
in the normal population
The incidence of
synchronous (multiple primary cancers happening simultaneously) and
metachronous (multiple cancers happening at intervals) CRCs happen in
up to 50% of individuals with Lynch syndrome, compared to less than
20% risk in patients with sporadic CRC
Also, CRC in Lynch
syndrome patients often happens in the right or proximal colon in
contrast to predominance of sigmoid or distal carcinomas in sporadic
Pathologic features of
Lynch syndrome-linked CRC often are:
2. Crohn's like
3. Signet ring cells,
features of Lynch syndrome are less normally found in sporadic CRC
and often are red flags for Lynch syndrome
There is a contentious
link between Lynch syndrome and breast cancer.
Evidence showed 50% of
breast cancers occurring in Lynch syndrome mutation carriers had a
loss of mismatch repair proteins
Lynch syndrome is a
probable diagnosis when multiple people on the same side of the
family diagnosed with colorectal cancer.
Also, cancer tends more
likely to be diagnosed at a young age.
The average age for
colorectal cancer to be diagnosed in a person with Lynch syndrome is
45 in contrast with the average age of 72 for a new diagnosis of
colorectal cancer in the general population.
In Lynch syndrome,
colorectal cancer is rather more likely to form on the right side of
ASCO advises tumor
testing for Lynch syndrome in all patients with colorectal cancer.
As another option,
tumor testing is advised for people who develop colorectal cancer in
patients younger than 70 or those who are older than 70 and have any
of the revised Bethesda guidelines.
There is also a higher
danger of a person with Lynch syndrome to form multiple cancers
during his or her lifetime
What are the causes of
Lynch syndrome is a
genetic disorder, indicating that the cancer risk can be passed from
generation to generation in a family.
Several genes have been
identified that are linked to Lynch syndrome.
They are MLH1, MSH2,
MSH6, PMS2, and EPCAM.
(modification) in any of these genes causes the person to have a
higher lifetime danger of forming colorectal cancer and other related
Women also have a
higher risk of forming endometrial and ovarian cancers.
Most mutations that
cause Lynch syndrome are present in the MLH1 or MSH2 genes.
Not all families that
seem to have Lynch syndrome will have mutations in MLH1, MSH2, MSH6,
PMS2, or EPCAM.
Some people will have
alterations in these genes that are not passed on in the family, but
are linked to the increasing age progression and other causes that
are not well known.
If a tumor is
discovered to have changes in these genes, the person’s blood will
also be tested for that abnormal gene.
If the blood and tumor
both have the changed gene, the disorder is inherited rather than
acquired, meaning other family members could be involved; testing is
How is Lynch syndrome
Normally, every cell
has two copies of each gene: one inherited from the mother and one
inherited from the father.
Lynch syndrome stays on
an autosomal dominant inheritance pattern, in which a mutation needs
to happen in only one copy of the gene for the person to have a
higher risk of getting that disease.
This indicates that a
parent with a gene mutation may transmit along a copy of their normal
gene or a copy of the gene with the mutation.
Thus, a child who has a
parent with a mutation has a 50% chance of getting that mutation.
A brother, sister, or
parent of a person who has a mutation also has a 50% chance of
getting the same mutation.
There are alternatives
for couples who wish to have a child when they know that one of them
has a gene mutation that raises the danger for this hereditary cancer
genetic diagnosis (PGD) is a medical test done in conjunction with
in-vitro fertilization (IVF).
It permits people who
carry a specific known genetic mutation to have children who do not
have the mutation.
A woman’s eggs are
taken and fertilized in a laboratory.
When the embryos reach
a certain size, one cell is taken out and is tested for the
hereditary disorder in question.
The parents can then
choose to implant embryos that do not have the mutation.
PGD has been in use for
over ten years, and more recently has been done for several
hereditary cancer predisposition syndromes.
It is a complicated
procedure with financial, physical, and emotional factors for couples
to note before starting
Lynch syndrome is a
genetic disorder caused by germ line mutations or alterations in any
one of the four genes known as mismatch repair (MMR) genes
MMR genes are necessary
to maintain the integrity of the DNA, examining for and correcting
mistakes that if not repaired have the possibility for tumor
formation and cancer development
The four MMR genes
indicated in the Lynch syndrome are MLH1, MSH2, MSH6, and PMS2
Lynch syndrome is
transmitted in a Mendelian autosomal-dominant (AD) pattern of
inheritance whereby individuals with Lynch syndrome have a 50% chance
of transmitting the genetic mutation to each of their offspring.
Patients with Lynch
syndrome are born with a normal functioning gene (wild type allele)
on one chromosome and a mutated gene on the other chromosome
In spite of the
presence of a Lynch syndrome-linked gene mutation at birth (the first
hit), cancer does not occur unless there is a loss of function (or
acquired somatic mutation) on the remaining chromosomal gene or
allele (second hit)
This acquired mutation
tends to be likely because of gene or environment interaction and
results in a second hit that immobilizes the remaining wild-type
The second hit leads to
the development of cancer due to the loss of the protective repair
mechanisms of the MMR genes
The need for the second
hit demonstrates why some patients with the genetic mutation might
not form Lynch syndrome-linked cancers
Patients with a high
risk of Lynch Syndrome should be presented with annual or biannual
colonoscopies from the age of 25 years
How common is Lynch
Most colorectal cancer
is sporadic, meaning it occurs by chance with no known cause.
Lynch syndrome is
responsible for about 2% to 5% of all cases of CRC (colorectal
What are the symptoms
and signs of Lynch syndrome?
One set of criteria
used to recognize Lynch syndrome is called the revised Bethesda
colorectal cancer younger than age 50
2. Forming colorectal
and other cancers linked with Lynch syndrome individually or together
(colorectal cancer, endometrial cancer, small bowel, and ureter, or
renal pelvis cancer, ovarian cancer)
colorectal cancer with tumor features linked to Lynch syndrome at an
age younger than 60
4. Colorectal cancer
presence in one or more first-degree relatives who also has or has
had another Lynch syndrome-linked cancer, with one of these cancers
forming before age 50.
5. Colorectal cancer in
two or more first- or second-degree relatives with another Lynch
The definition of Lynch
syndrome is still developing.
A family may still have
Lynch syndrome even if the revised Bethesda guidelines do not fully
comply with the family history.
Consultation with a
doctor who has training in genetic diseases and disorders, such as a
genetic counselor or medical geneticist, is advised for people who
have a family history that indicates Lynch syndrome.
There are two different
forms of Lynch syndrome called Muir-Torre syndrome and Turcot
How is Lynch syndrome
Lynch syndrome tends to
be likely if a family history meets the revised Bethesda guidelines
Lynch syndrome can also
be established through a blood test.
The test can detect if
someone has a mutation in one of the genes linked with Lynch
Presently testing is
provided for the MLH1, MSH2, MSH6, and EPCAM genes.
The PMS2 gene is tested
for in some medical trials (research studies) and cancer centers that
specialize in Lynch syndrome.
Not all families with
Lynch syndrome will have a mutation in one of these genes.
For patients who have a
family history that indicates Lynch syndrome, screening tests can be
done on tumor (cancer) tissue to help detect if Lynch syndrome is
The two screening tests
indicated are micro-satellite instability testing (MSI) and
immuno-histo-chemistry testing (IHC).
The results of these
tests can show whether more specific genetic testing should be done.
Since most colorectal
cancer is sporadic, genetic testing is only advised for people who
have a family history that indicates Lynch syndrome.
Testing for mutations
in the Lynch syndrome genes may not be advantageous for the average
What is the evaluated
cancer risks linked with Lynch syndrome?
General cancer risks
for people with Lynch syndrome are:
1. Colorectal cancer:
*Up to 80%
2. Stomach cancer: 11%
3. Hepatobiliary tract
cancer (liver/bile duct): 2% to 7%
4. Urinary tract
cancer: 4% to 5%
5. Small bowel cancer
(intestines): 1% to 4%
6. Brain or central
nervous system tumor: 1% to 3%
*The estimated lifetime
risk of colorectal cancer in people with Lynch syndrome has a wide
range, with 80% being the very upper limit of that range.
danger evaluations are for people with Lynch syndrome who do not
have regular colonoscopy screenings.
Regular screenings with
colonoscopy considerably decreases this risk.
Cancer dangers for
women with Lynch syndrome are:
1. Endometrial cancer
20% to 60%
2. Ovarian cancer 9% to
Lynch syndrome has been
linked to higher risk of other types of cancer as well, such as
pancreatic, prostate, kidney, and breast cancers.
1. Colonoscopy every 1
to 2 years, beginning between the ages of 20 to 25 or 2 to 5 years
younger than the youngest age at diagnosis of CRC in the family,
whichever is sooner
2. Testing and
treatment for Helicobacter pylori is advised if a person has been
diagnosed with Lynch syndrome
Screening for other
cancers linked with Lynch syndrome may be advised depending on a
person’s family history.
Screening for women
1. Yearly pelvic
examination, transvaginal ultrasound, endometrial biopsy, from age 30
Women who do not wish
to have any more children may want to think having preventive surgery
to remove the uterus and ovaries.
Screening methods may
change over time as new technological procedures are developed and
more is known about Lynch syndrome.
It is important to talk
with the doctor about suitable screening tests.
What is the treatment
for Lynch Syndrome?
Removal of the entire
colon is the only way to completely avoid the development of colon
cancer or to treat a present colon cancer.
surgeries are presently present for the treatment of Lynch Syndrome.
The 3 most often
performed surgeries are:
1. Subtotal colectomy
with ileorectal anastomosis
2. Total colectomy with
ileoanal pull-through (pouch procedure)
3. Total colectomy with
Subtotal colectomy with
ileo-rectal anastomosis and post-surgical rectal surveillance are
advised when colorectal cancer forms in patients with Lynch Syndrome.
This surgery may be
regarded for prevention in selected mismatch repair (MMR) gene
Subtotal colectomy with
ileo-rectal anastomosis is favored over segmental resection or
hemicolectomy for Lynch Syndrome-linked cancers that occur proximal
to the peritoneal reflection.
Even though total
procto-colectomy with ileo-anal anastomosis and total
procto-colectomy with ileostomy remove the need for endoscopic
surveillance, these interventions are normally reserved for patients
with Lynch Syndrome who manifest with rectal cancers, mainly because
of concerns about post-surgical morbidity and quality of life
What is the prognosis
of Lynch Syndrome?
The 5-year survival
rate in patients with Lynch Syndrome is evaluated to be about 60%,
compared with 40-50% for sporadic cases.
Colorectal tumors that
have micro-satellite instability (MSI)-positive have specific
features, such as a tendency to arise in the proximal colon,
lymphocytic infiltrated, and a poorly differentiated, mucinous or
signet ring appearance.
Doctors have found that
MSI-positive tumors are linked with better survival rates.
Based on the stage of
the cancer, patients with colorectal cancer from families with a
history of Lynch Syndrome have a better prognosis than patients with
colorectal cancer in the general population (sporadic colon cancer),
which may be enlightened by immunological factors.
with colon cancer have shown that tumors affect the host immune
response by changing host T-cell receptors
The defective T-cell
response was seen only in animals with chronic tumors, indicating
that rapid tumor growth, as observed in Lynch Syndrome, may preserve
Colorectal cancer was
decreased by 62% in the screened group versus the unscreened group.
The decrease was
believed to be due to polypectomies in the intervention group.
non-polyposis colorectal cancer (Lynch Syndrome) is the most frequent
form of hereditary colorectal cancer.
It is passed on in the
family as an autosomal dominant syndrome as a result of defective
mismatch repair (MMR) proteins.
Lynch Syndrome is
responsible for 2-5% of all colorectal carcinomas.
Over 90% of all
colorectal cancers in Lynch Syndrome patients show a high
micro-satellite instability (MSI-H), which indicates at least 2 or
more genes have been mutated (modified) in Lynch Syndrome families or
atypical Lynch Syndrome families.
Colorectal cancer in
patients with Lynch Syndrome occurs at a younger age than in the
general population and is featured by:
1. A higher danger of
other cancers, such as endometrial cancer and,
2. In a lesser extent,
cancers of the ovary,
4. Small intestine,
5. Hepatobiliary tract,
7. Upper urinary tract,
9. Brain, and
Lynch Syndrome is
1. Lynch syndrome I
(familial colon cancer) and
2. Lynch syndrome II
(HNPCC linked with other cancers of the gastrointestinal [GI] or
The higher cancer risk
is due to inherited mutations that corrupt the self-repair capability
The tumor testing
(i.e., immuno-histo-chemistry, MSI, germ-line testing, and BRAF
mutation testing), screening, and prophylactic surgery all assist to
decrease the risk of death in patients with HNPCC or Lynch syndrome.
The advantages of all
methods of tests mainly affect relatives with a mutation linked with
HNPCC or Lynch syndrome.
application of colorectal tumor testing helps to recognize families
with HNPCC or Lynch syndrome.
testing could produce considerable advantages at reasonable cost.
1. Mainly in females
with a mutation linked with HNPCC or Lynch syndrome that begin
regular screening and have reducing surgery.
cost-effectiveness of such testing is dependent on an increased rate
in relatives at danger for HNPCC or Lynch syndrome.
An inherited mutation
in one of the DNA mismatch repair (MMR) genes appears to be a
critical factor in Lynch Syndrome.
MMR genes normally form
proteins that recognize and correct sequence mismatches that may
happen during DNA replication.
In Lynch Syndrome, an
abnormality that stops activation of an MMR gene leads to the
collection of cell mutations and largely raises the tendency of
malignant transformation and cancer.
Doctors have recognized
7 distinct MMR genes, such as:
hMLH1 on band 3p22
hMSH2 on band 2p16 - 45-50%
hMSH6 on band 2p16: 10%
hPMS1 on band 3p32 - Rare
on band 7q22 - 1%
Other mutations are:
on band 5q14.1 - Rare
EXO1 on band 1q43 - Rare
Mutations of hMLH1
and hMSH2 are
responsible for about 70% of MMR mutations in Lynch Syndrome.
10% affect hMSH6.