It’s As Easy as Pulling a Hair – SHGC/Kaiser Permanente
A
RE YOU AT RISK FOR BRAIN CANCER?
FIND OUT NOW…
IT’S AS EASY AS PULLING A HAIR!
Research has discovered a link between a particular gene marker and brain cancer. With the help of a
simple test that we have developed, you can set your mind at ease over whether you might be at risk.
Studies indicate that you are at greater risk for brain cancer if any close relatives have suffered from the
same disease. By using this test, you can determine your true level of risk—otherwise, it’s just a guessing
game.
Simply complete the form below, mail or fax it to us, and we will send you the materials to collect your own
DNA sample. You can do this in the comfort and privacy of your home and will receive the results within two
weeks.
For just $250, you can purchase peace of mind. Don’t you want to know?
-------------------------------------------------------------------------------------------------------------------BRAIN-LINKED MARKER (BLM1) DIAGNOSTIC TEST REQUEST FORM
Jackson
Last Name
Nicholas
First Name
N.
Middle Initial
740-398-4562
Phone
Nnjack@funnet.com
Email
740-398-4500
Fax
608 Madison Street
Street Address
Detroit, MI
City & State
48105
Zip
Male/Female (please circle one)
8-25-64
Date of Birth
555-44-3333
Social Security Number
Mail to:
WeCare Testing
11011 Surfrider Way
Sunset, CA 95000
OR
Include check or money order
for $250 made out to WeCare
Testing
Fax to: (credit card orders only)
809-999-9999
Credit Card: Visa/Mastercard
Number
x
Cardholder’s Signature
Exp.
By signing below, I consent to have this test conducted on my behalf and do not hold WeCare Testing liable:
x Nicholas N. Jackson
10-30-98
Signature & Date
WeCare Testing
BLM1 DIAGNOSTIC TEST RESULTS
1-888-999-9000
Client Number: WCT555-44-3333
Name: Nicholas N. Jackson
Your BLM1 test results were: positive
DOB: 8-25-64
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It’s As Easy as Pulling a Hair – SHGC/Kaiser Permanente
Nicholas twisted nervously in his chair. He had come
to see Mary Ann, a genetic counselor, after receiving
the results from his mail-in test. When he received his
positive test results, he panicked. “What does this
mean?” he thought to himself “and what can I do
about it?” He immediately called his doctor who
recommended that he meet with a genetic counselor.
Now, as he sat in Mary Ann’s office, he was prepared
for the worst—after all, his grandfather had died of
brain cancer at age 42. Mary Ann looked puzzled as
she reviewed the documentation that Nicholas
brought with him. His original test request form and
test results provided no explanations. “Did WeCare
include any additional information?” she asked.
Nicholas replied that he had only received the test
results with no further elaboration.
Genetic Counseling
Genetic counselors help people who are at
increased risk for, or who have a family history
of, an inherited condition or conditions. They also
counsel people who are affected with or who
have family members with birth defects, mental
retardation, or genetic syndromes. In order to
provide someone with information about the
condition in question, assess that person’s
unique risks, and offer supportive counseling,
genetic counselors often must: analyze
inheritance patterns; review pertinent medical
records; order appropriate tests and interpret the
results; and review available options and
resources for further diagnosis, treatment or
support.
Why did Nicholas’ doctor refer him to a genetic counselor? What information
could WeCare have provided to help Nicholas understand his test results?
A Little Detective Work: How Are Tests Developed?
First, Mary Ann took a detailed four-generation pedigree (a medical family tree) and got a sense
of Nicholas’ concerns and his level of anxiety. She immediately and calmly began reassuring
him that there was not yet any reason to panic, and explained that she would need to do some
detective work to determine how to interpret his test results. Although Nicholas’ grandfather had
died of brain cancer and Nicholas’ own test results were positive, these facts did not
automatically mean he would get cancer. It was more likely that the positive finding in his test
results merely indicated, if anything, that he had a somewhat higher than average risk of
developing brain cancer sometime in his lifetime—not that he was guaranteed to get brain
cancer. Mary Ann would have to determine the actual level of his risk, and she could only do this
by finding out the nature of this particular test; the conditions under which it was developed; its
validity, sensitivity, and specificity; and its predictive value. “At this point,” she told Nicholas,
“we don’t know much more about your risk for developing brain cancer than we did before you
received your test results.”
This diagnostic test was new on the market, and Mary Ann and her colleagues had no experience
interpreting the results. Nicholas was the first patient she encountered who had used this test. She
knew that diagnostic tests such as this one were often based on findings from a genome database
mining company. These mining companies discover associations between given diseases and
various gene markers that they find (“mine”) through analyzing information in genome
databases. This information can be licensed or sold to a diagnostic testing company. Once an
association has been established (i.e., the testing company finds that a relevant percentage of the
population with the gene marker is eventually diagnosed with the disease), they then provide the
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It’s As Easy as Pulling a Hair – SHGC/Kaiser Permanente
general public with testing services to determine whether someone has a higher than background
risk for the disease in question. To further determine the nature of the association between the
disease and the gene marker, the diagnostic testing company must run “population studies” to
determine the proportion of people who:
 have this particular gene marker and have the disease in question, and
 have this particular gene marker but do not have the disease in question.
This information can then be sorted by age groups to begin to get a better sense of how often the
marker is associated with the disease in question.
Ideally, population studies are carried out with large numbers of participants (often thousands or
more depending on how often the disease occurs). Population studies are needed to determine
whether there really is a connection between the gene
marker and the disease and how strong that
The Human Genome Project
connection appears to be. A longitudinal study (a
The Human Genome Project’s mission is to
study over a period of time such as 10 or 30 years) is
construct maps (both physical and genetic) of the
the most accurate way to discover how many people
human genome (our complete set of genetic
instructions), which will allow us to understand
with a given marker actually develop the disease over
DNA and its role in heredity and disease more
time. However, this type of study takes a very long
fully. Centers for undertaking this research are
time and most companies want to get their tests on
located worldwide. By determining the sequence
the market long before these study results are
of the chemical constituents of DNA (bases
available.
known as A, G, C, and T), we can identify gene
markers (segments of DNA) that serve as sign
posts for the location of genes—particularly those
responsible for various diseases.
Therefore, other quicker types of studies are used to
get a general sense of the risks associated with a
given marker. One type of quick but less accurate
study is called a “general population survey with age
stratification.” A large number of randomly chosen individuals in the general population is tested
for a given marker and their medical histories and ages are recorded. Comparisons are made
between the number of individuals with the marker who have ever had the disease in question
(separated by age) and the number of individuals with this marker who have not had the disease
(separated by age).
The study also needs to include the number of people without the marker who have the disease
and the number of people without the marker who don’t have the disease. Separating the data by
age and making comparisons between age groups can help the company get a feel for the
percentage of people with the marker who actually develop the disease without waiting for the
results of longitudinal studies. For example, looking at the rate of a disease in a sub-population
of 70 or 80 year olds may give more information about the percentage of unaffected individuals
with the marker than a sub-population of 20 year olds. Another way to separate the test data is to
look at people with a family history of the disease and those without and compare how many
individuals in each category have the marker.
Companies are often anxious to get diagnostic tests such as BLM1 on the market because they
believe they are providing a valuable service to the public—in some cases, having information
about one’s level of risk for a disease can lead to prevention or control through lifestyle changes.
In fact, Mary Ann knew that WeCare also marketed a test that can determine whether a person
has a genetic predisposition for adult-onset diabetes that had helped thousands of people lower
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It’s As Easy as Pulling a Hair – SHGC/Kaiser Permanente
their chances (or risks) for developing diabetes through exercise and monitoring their diet. Thus,
these diagnostic companies do provide a valuable service.
What is a population study? How valid would it be to generalize a study
conducted in your classroom to the population at large (i.e., the world)? Take
a poll of your classmates: how many classmates can roll their tongues? To
what extent can you assume that the numbers you find in your classroom mirror
the world? Why or why not? What factors—or controls—do you need to
consider?
The Development of the WeCare Brain-Linked Marker (BLM1) Test
Mary Ann’s next step was to investigate the development and nature of WeCare’s Brain-Linked
Marker (BLM1) test. She contacted WeCare and asked them to describe their population studies.
She discovered that WeCare, in a hurry to get the test on the market, only conducted the study
over the course of several months. Moreover, their only study was limited to 20 adult male
patients suffering from brain cancer. Of these 20 patients, all were tested and found to have the
BLM1 marker. No studies were conducted with a random population of “healthy” subjects.
Healthy test subjects include both (1) those who do not show signs of brain cancer but are known
to be at risk because of family history and (2) those who do not show signs of brain cancer and
have no known risk for getting brain cancer.
As a class, make a table of Mary Ann’s findings about the BLM1 test.
Confronting WeCare
Mary Ann recognized that the BLM1 test was
FDA regulation of tests
offered as a service rather than as a kit and therefore
was not regulated by the Federal Drug The FDA only regulates tests marketed as kits
Administration (FDA). This meant that there would and not those marketed as services. An example
be no regulatory organization to contact regarding of a kit is the glucometer strip used to test for
concerns she had about the BLM1 test. These diabetes. In this case, clients receive a kit that
allows them to not only collect blood to test, but
concerns included the limited study population, the
also to carry out the test themselves with
lack of randomized population studies and the lack
immediate results—all done at home. In the case
of risk information provided to clients about the test of WeCare’s test for BLM1, the client only collects
results. She decided to confront WeCare directly a DNA sample and then sends it to WeCare’s
with these concerns about their methodology. She laboratory for analysis. This test, then, is actually
was relieved by their concerned response. They had
a service provided by WeCare, given that WeCare
received a large number of complaints similar to
determines the existence of the gene marker in a
Mary Ann’s and had begun a number of appropriate
laboratory rather than making it possible for the
client to conduct the actual test at home.
population studies with much larger sample sizes.
From now on, they assured her, all marketing and
test results would include more detailed interpretation, particularly as their study provided better
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It’s As Easy as Pulling a Hair – SHGC/Kaiser Permanente
risk estimates. They were quite concerned about their credibility and their responsibility to their
clients.
Mary Ann’s Follow-Up Counseling with Nicholas
Nicholas was still awaiting an analysis of his test results. Mary Ann called him and explained her
findings, restating that Nicholas still had no more knowledge about his true risk level than he did
before receiving his test results. She suggested a repeat genetic counseling appointment
sometime in the future when WeCare completed their population studies. She mentioned that
WeCare had promised to supply her with their study data as it became available and she
reassured him she would contact him at that time.
Mary Ann counseled that, in the meantime, Nicholas should monitor his health as usual through
regular check-ups, maintain an ongoing relationship with his health care provider, and report any
unusual symptoms such as severe headaches or loss of vision. She added that while there was
currently no cure for brain cancer, early detection was still important and that research on more
effective treatments holds much hope for the future. “Although it’s not known for sure that a
healthy lifestyle lowers the risk for brain cancer, it is always a good idea to maintain normal
body weight, eat a low-fat, high fiber diet and get plenty of aerobic exercise—and avoid
smoking.”
She ended the call by asking him about his reactions throughout the whole process and his
current anxiety level. Nicholas replied that he had been incredibly shocked and felt doomed and
helpless when he first got his test results. After learning that the test couldn’t actually tell him his
risk to develop cancer, he still felt somewhat unsettled and worried. He told Mary Ann that
although his life is more or less back to normal, if he had it to do all over again, he never would
have taken that test!
Your task is to design a population study as a team member in the test
development division of WeCare. What groups should you represent in your
population study? What factors do you need to control for (revisit the table you
created to organize Mary Ann’s findings—what other factors should you
consider?)?
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