Study: The Testing Process
Amanda Ewart Toland,
by Miriam Komaromy,
testing process has many steps that ensure a people
have a full understanding of the benefits, risks and
implications of the test results both for themselves
and for their family. The steps to genetic testing include:
review the entire process, consider the case of 35 year
old Mary, whose mother died of colon cancer at age 50,
whose cousin died of colon cancer at age 45, and whose
uncle was diagnosed with colon cancer a year ago (at
age 52). In this example you will see all of the different
pieces of the genetic testing process.
if A Genetic Test Is Appropriate
doctor suggested that she collect medical records
from her family members to help confirm the history
first question that should be asked is, "Is genetic
testing appropriate?" For Mary and her doctor the
first step to answering that question was the collection
of Mary's family medical history.
Mary had to call a few relatives to confirm cancer
diagnoses and the ages that people were diagnosed with
the cancer. While talking to her aunt, she found out
that another cousin had been diagnosed with endometrial
cancer. Mary's doctor suggested that she collect medical
records from her family members to help confirm the
history. To do this, Mary sent medical release forms
to the hospital that treated her mother and to her living
uncle with cancer.
review of Mary's history, it was clear to her doctor
that there were many people in her family who had developed
colon cancer at an early age. Mary's doctor felt that
the pattern of cancers seen (colon and endometrial)
fit a pattern of Hereditary
Nonpolyposis Colorectal Cancer (HNPCC).
For HNPCC, there is a screening test called MSI
testing that may
be done before genetic testing. A positive MSI test
gives clues that there may be an HNPCC mutation.
MSI testing is done on tumor
samples. Mary's doctor explained this test to Mary and
the implications for her and her family. Because Mary
herself did not have cancer, Mary's doctor (with Mary's
permission) requested tumor tissue from Mary's mother's
tumor for MSI testing from the hospital where she had
her colon cancer surgery. After a few months, the results
from MSI testing were completed. Mary's doctor explained
that Mary's mother's tumor was MSI-high, which suggested
that her mother might have had a mutation in one of
the genes causing HNPCC.
The next question was who in the family, if anyone,
should be tested for the actual genes involved in HNPCC.
Mary wanted to be tested, but her doctor explained that
if she tested negative they would not know if she was
negative because she did not inherit the mutation in
the family or if the mutation was in a gene that was
not being tested. Mary agreed to ask if her affected
uncle Evan would be willing to go through genetic testing
first. If Evan tested positive, then Mary could go through
testing. Evan agreed to consider testing, but wished
to be seen at a medical facility closer to where he
lived. Mary's doctor suggested the name of a cancer
center close to where Evan lived.
and his wife met with a genetic counselor
at the cancer center to learn more about genetic testing
and hereditary cancer. The genetic counselor explained
what HNPCC was, how genes are inherited, what a mutation
is, and other basic genetics relating to hereditary colon
cancer. She reviewed different outcomes for the testing:
a positive test, a negative test, and an indeterminate
test result. She also discussed different options available
to individuals who test positive and medical recommendations
for Evan if he were to test negative.
Evan's wife was worried about how this might affect their
children and grandchildren. One of their children had
previously died of colon cancer and another one had endometrial
cancer. They had a third child who had not had cancer.
The genetic counselor explained that if the test result
was positive that their living children could be tested
for the mutation in the family. If it was negative, they
would be "off the hook" and back to population
risk. If the test was positive, surveillance guidelines
would be recommended for them.
wife worried about how genetic testing might affect
their children and grandchildren.
Evan asked about insurance discrimination based on genetic
testing. The counselor said that although there were no
good studies showing that genetic discrimination happened,
they could keep his result confidential if he did not
use his insurance to pay for the test.
Evan and his wife reviewed their concerns and questions
with the genetic counselor. Evan wanted black and white
answers: should he be tested or not. However, the genetic
counselor could only tell him that this was a very personal
decision and should be made based on and what benefit
it might provide for Evan and his family, and with a thorough
understanding of the risks involved. Ultimately, Evan
decided to go through genetic testing for HNPCC to benefit
his children, grandchildren, nieces and nephews.
the test, Evan had a tube of blood drawn by the nurse
in the laboratory near the genetic counselor's office.
He decided to pay for the test himself by using a credit
card. Before sending the sample by Federal Express to
the laboratory where the testing was to take place,
the genetic counselor checked that the name on the tube
was correct. The genetic counselor also included brief
information on the family history for the laboratory.
the sample arrived, the laboratory technician logged
in the sample and gave it a laboratory identification
number. She also checked which test was being requested
and checked to ensure that the family history matched
the request. The next day DNA
was extracted from the tube and over the next few weeks
the lab sequenced the common genes that cause HNPCC.
When a change was found in one of his genes, the laboratory
resequenced the DNA to confirm their result. To further
ensure accuracy, the laboratory director reviewed the
data and the result, and double-checked all the identification
numbers. The result was sent back to Evan's genetic
counselor with an explanation that the change in the
gene was likely to be the cause of Evan's syndrome.
to the genetic counseling clinic to receive his genetic
test result. His niece Mary and his wife came with him.
The genetic counselor that had seen Evan before told him
that his genetic test had come back positive. There was
now a known mutation in the family that could explain
the colon and endometrial cancers. The genetic counselor
reviewed the value of this test. Evan is at increased
risk for a secondary colon cancer. Because of this, it
is recommended that he have regular colonoscopies.
He is also at slightly increased risk for some upper GI
genetic counselor that had seen Evan before told
him that his genetic test had come back positive.
The counselor explained that this mutation was likely
the cause of the colon cancer and endometrial cancer seen
in two of Evan's daughters. She recommended that his two
living children get screening for HNPCC-related cancers.
was upset that he had passed on a faulty gene to his daughter
who had died of colon cancer, his wife consoled him that
now they could do something to protect their two younger
Evan could do something to protect his children.
of Results to Other Family Members
Evan was found to have a mutation known to cause HNPCC,
other relatives in his family could now be tested for
the same mutation. The genetic counselor reviewed the
pros and cons of genetic testing for Mary. If Mary tested
negative for the mutation in the family, she would be
at the same risk for colon cancer as other people in the
general population. If she carried the same mutation as
her uncle, Mary would be at elevated risk for colon, ovarian,
and endometrial cancers and would be recommended to undergo
vigilant surveillance for those cancers. Mary decided
that she would benefit from testing.
Mary had her blood drawn and sent to the same laboratory
that conducted the testing for her uncle.
Because the laboratory only needed to look for the one
mutation in the family rather than screening the genes
for HNPCC for mutations, the test was less expensive and
much quicker. After a few weeks, Mary met with her doctor
for results of the test. She did not inherit the mutation
that her uncle and mother had shared.
that the mutation was known, testing could be faster
and less expensive.
Other family members, such as Mary's brother and sister,
however were still at risk for inheriting the mutation.
With her doctor's help, Mary drafted a letter to send
to all of her at risk family members. The letter discussed
the family's increased risk for colon and other cancers
and that testing was available. Contact numbers for Mary
and the cancer center where Evan had his testing were
Mary's sister Alice decided to have testing. Her brother
Tom decided that he would not have testing at this point,
but would have regular colonoscopies for screening. Alice
was found to carry the same mutation in the HNPCC gene
as her uncle.
drafted a letter to send to all of her at risk family
Evan and Alice tested positive for a known mutation, they
were given specific medical recommendation for cancer
screening. They were also told about a clinical
trial involving a drug, similar to aspirin, that was
thought to slow down the growth of precancerous polyps.
Alice was interested in learning more about clinical trials
and her doctor provided her with information.
In addition to regular medical care, Evan and Alice were
encouraged to call their doctor or the cancer center annually
to find out if anything new was known about HNPCC. Because
genetic testing is new and medical information on genetic
disorders is evolving, family members and individuals
who have gone through testing need to keep in contact
with medical personnel who can update them on any changes.
For affected individuals who tested negative, additional
genetic tests may be offered if new genes are discovered
that are involved in that disorder. Also, medical interventions
and recommendations will change over time as more is learned
about the effectiveness of various preventative and treatment
strategies. Some testing centers may offer the latest
in clinical trials or be able to relay the results of
clinical trials that are relevant to mutation carriers
or high-risk individuals.
members and individuals who have gone through testing
need to keep in contact with medical personnel who
can update them on any changes.
In addition to keeping in contact with your doctor and
local cancer center, you can also keep informed of new
treatments, discoveries, and clinical trials by becoming
a member of Genetic Health.
J. et al. (1992). A case-control study of screening
sigmoidoscopy and mortality from colorectal cancer.
New England Journal of Medicine 326(10): 700-2.
Mandel, J. et al. (1993). Reducing mortality from colorectal
cancer by screening for fecal occult blood. Minnesota
Colon Cancer Control Study. New England Journal of
Medicine 328(19): 1365-71.
©Copyright 2011 Latest Medical, Inc.. All Rights Reserved.