By Deborah Borfitz
October 29, 2018 | An estimated 100
million-plus people, roughly one-third of the U.S. population, will
have had their DNA analyzed using an at-home genetic test kit by 2021. Up to 60%
of the time, identified genetic variants are going to be proven correct with
retesting in a medical-grade laboratory. For an investment starting at under $100,
individuals can learn things that might save their life—or cause them to have unneeded
treatments and surgeries—without a physician’s order for the test and often
without follow-up of any kind by a healthcare professional.
There’s no use in physicians simply
ignoring the soaring popularity of direct-to-consumer (DTC) genetic tests, says
Emily Fine, a gynecologist in Hamden, Connecticut who is affiliated with
Yale-New Haven Hospital. Ready or not, patients have started showing up at
doctors’ offices with their 23andMe
and Ancestry findings
and possibly also beliefs about next steps from Dr. Google.
Fine believes that as DTC
genetic tests become more popular and affordable, physicians ought to be
proactively asking patients if they’ve had one done during routine exams—and
then counseling them that it’s “only a first step” and to be sure they’re
properly educated about what the results do and don’t mean, and the role of
other factors (e.g., environmental and lifestyle) on disease risk. “A lot of my
patients are already sharing that information with me,” says Fine.
“The problem with DTC genetic
tests is that you can’t babysit ramifications of some of the information,” she
adds. “I have a patient who found out she’s at risk for Alzheimer’s, and now
she is profoundly depressed and every time she forgets where she put her keys
she is ready to shoot herself.”
Fine’s preference is to
understand patients’ pedigree or family history before ordering any clinically-indicated
genetic test. But findings of DTC tests can sometimes also change her medical recommendations,
she says. Recently, for example, a patient with a relatively weak family
history of breast cancer discovered via 23andMe that she was of French-Canadian
descent—an ethnic group that put her at heightened risk of several
cancer-causing genetic mutations. That prompted Fine to refer the woman to have
her entire cancer genome mapped.
The trouble is most physicians aren’t
like Dr. Fine. They don’t understand genetics well enough to lead the
conversation, if they have the time or even believe in the clinical utility of
DTC consumer testing at all. “It is usually hard to get an appointment with a
specialist based on 23andMe results,” notes genetic counselor Dawn Laney,
director of the Emory Genetic Clinical Trials Center. Laney is also co-founder
of ThinkGenetic, focused on educating
bewildered patients and connecting them with personalized clinical genetic
counseling and testing services.
23andMe findings are based on a
SNP panel that offers an
incomplete view of disease susceptibility, says Laney. To assess breast cancer
risk, for example, 23andMe relies on three genetic markers in the DNA—including
BRCA1 and
BRCA2. Detected gene changes require follow-up in a diagnostic
laboratory that specializes in breast cancer genes to determine if an
individual’s lifetime risk is negligibly or profoundly higher than average. The
opportunity for needless worry only multiplies when patients opt to receive all
their raw uninterpreted genotype data from 23andMe and upload it to online
portals such as Promethease for a personal DNA report.
Ellen Matloff, president &
CEO of digital health company My Gene
Counsel, says she was adamantly opposed to DTC testing just six
years ago. But since then, 15 million people have had one done, and the number
of DTC genetic companies has mushroomed. “I realized, especially as a genetic
counselor, I was doing consumers a disservice with my attitude. What we needed
to do was find a way to use information from these tests to create a bridge for
patients to the medical world.” My Gene Counsel is endeavoring to do that by
becoming a trusted source of unbiased, evidence-based information for patients
and physicians.
Some of Fine’s patients,
including those with genetic mutations of unknown significance or who are BRCA-negative
but have a concerning family history of breast cancer, were among the first to
register. Other early adopters are BRCA-positive patients anxious to know how
they will be monitored and what risk-reduction measures they can take.
Knowledge Gaps
23andMe and Ancestry dominate the “entertainment testing”
market, telling people everything from their origins to genetic traits like
curly hair and caffeine sensitivity, says Laney. But 23andMe is also now
FDA-approved to assess their customers for seven rare genetic conditions such
as Gaucher disease and alpha-1
antitrypsin deficiency as well as genetic predispositions for
additional conditions, including breast cancer, Alzheimer's, Parkinson's,
and celiac diseases. Helix has also moved in this direction
with DNA testing kits for diabetes and inherited high cholesterol. “I consider
these screening tests because they’re really designed to look for genetic
conditions that are actionable,” Laney says. “They’re more designed to suggest
the possibility of a problem, and then you’re supposed to get further testing
done at a doctor’s office.”
A growing number of DTC
companies have also expanded into carrier testing, with implications for people
in their childbearing years. Anyone identified as a carrier for a
condition by a DTC kit needs to have the finding verified in a more specific
diagnostic setting and receive genetic counseling to learn how the gene change
may increase the risk for problems in their children, Laney says. Some carrier
panels may also reveal an existing genetic condition or increased risk for a
health issue.
“It makes sense for patients to
share those results with their physician, mostly just to start the conversation,”
Laney says, although PCPs mostly still view 23andMe as more of a “delegated
annoyance.” Physicians should be at least be aware of the various DTC genetic tests
being marketed to their patients.
Genetics and clinical diagnostics
are related and, in some respects, overlapping fields. One big difference is
that genetics can sometimes find “previvors” who are genetically predisposed to
a disease, but do not yet have it. The advantage of knowing a person’s genetic
predispositions before any sort of symptoms emerge is that physicians can work
with patients to reduce their risk of disease or at least catch it at an
earlier, more treatable stage, says Matloff. The information would be useful to
the medical practices of primary care physicians (PCPs), OB-GYNs, breast
surgeons, oncologists, gastroenterologists, and cardiac specialists, among others.
Before founding My Gene
Counsel, Matloff ran the Cancer Genetic Counseling Program at Yale School of
Medicine for 18 years, and during her tenure the cost of medical-grade genetic testing
plummeted and was recommended more widely. It was also more often ordered by
healthcare providers without the help of a genetic counselor. “We started
seeing a lot of mistakes happening, bad mistakes, people who had their breasts
and ovaries removed and then later learned that they hadn’t needed to, and
people with advanced cancer diagnoses who were told their test was normal when
in fact it was not,” she says. At the same time, thousands of people began to
have DTC genetic testing and had their raw data in hand.
“I realized we needed to do
something different, something digital and scalable that would not replace in-person
meetings with physicians or a genetic counselor but that would be available
faster,” says Matloff. “It would be different from a WebMD search and tie
specifically to a person’s test result by gene and variant, and then send out
push notifications as the field and our information updates.”
Keeping Current
Anyone who has had BRCA1 or
BRCA2 testing can log onto My Gene Counsel to learn about their gene and
variant, and what they can do about the finding. Registered users of its
recently launched patient portal can have their genetic test results paired with
matching streams of information. For those who had testing done via a DTC kit,
that would include how to get results confirmed at a medical-grade testing
facility. In the next few months, all of the readily tested hereditary cancer
and cardiac genes will be released, says Matloff.
Users also receive push
notifications by text or email when any new evidence emerges about their
particular genetic mutation. That’s important, says Matloff, because many
people who have genetic testing done never return to a genetic counselor if
they saw one in the first place. “Right now, there is absolutely no mechanism
for patients to receive updates. They just have to hope that their healthcare
provider remembers to update them the next time they go in for a visit… and
that’s a tall order considering how many patients physicians are seeing and how
little time they’re able to spend with each one.”
Come early 2019, My Gene
Counsel will also be separately available as a portal for physicians, nurses,
physician assistants and other healthcare providers, including genetic
counselors, to look up specific gene mutations of their patients, says Matloff.
Patients who are My Gene Counsel users can also enable their providers to
receive the same relevant updates they do.
The new tool will require a lot
less of providers’ time and be the better option from a malpractice point of
view, says Matloff. Physicians would need hours, if not days, to exhaustively research
some topics on their own, and they “simply don’t have the time and resources to
[independently] stay on top of all of the updates.”
“Genetics is the most rapidly
changing field in medicine, bar none,” agrees Fine, “so being able to tap into
that database will be very helpful.” Over time, she imagines it could even
guide clinical decision-making about when targeted interventions such as prophylactic
surgery are justified.
Bridging the Divides
Consumers presented with
concerning DTC genetic test results need guidance on next steps and may not
know where to turn, says Laney. Most reports will instruct them to consider
genetic counseling, but not how to find an affordable and available counselor.
Test results can also be hard to
interpret, says Laney. Not long ago, a man who ran his raw data from 23andMe
through Promethease came into Emory’s genetic clinic for a consult and testing
only to learn his newly found genetic condition was a fluke, the result of a
glitch in the software. “He had a variant alright, just not a disease-causing
one,” she says. “If you’re a consumer that’s awfully confusing. All the
terminology is hard enough for someone who has gone through medical school to
understand.”
Part of ThinkGenetic’s mission,
Laney says, is to translate complicated genetic information into plain language
for the general population, so they enter the conversation with their PCP on a
more level playing field—not simply barrage them with a long list of questions.
“We’ve started with the conditions that are on carrier panels, have clinical
trials, or are very common in the population, things where we know there are
actionable next steps,” she says.
Admittedly, ThinkGenetic has a
“long way to go in reaching out to PCPs, family practitioners, and
neurologists/specialists,” says Laney. It has designed symptom-based,
patient-specific summaries with actionable next steps to help with
patient-doctor engagement so healthcare providers don’t get “blindsided” by
patients who initiate a conversation about their risk for a specific genetic
condition. But currently, the summaries cover only about 200 of 7,000 known
genetic conditions.
ThinkGenetic’s “patient-focused
diagnostic assistant” helps patients remember to mention critical signs and
symptoms to their physician, says Laney, since some seemingly unrelated
symptoms “could be key to knowing what’s going on with them.” An example
would be people with Fabry
disease, a rare genetic condition, where the important clues
would include GI pain, a burning sensation in their hands and feet, and an
inability to sweat normally.
For physicians, having a
targeted ThinkGenetic summary that tells them the ways a genetic condition like
Fabry disease can affect the whole body and the specialized treatment
facilities where they can refer patients “sounds a lot better than ‘I don’t
know’ or trying to bluff their way through it,” says Laney. After a confirmed diagnosis of a genetic
condition, ThinkGenetic’s summary content also provides healthcare providers
and consumers with useful “tips and tricks” (e.g., a foot mister that cools the
extremities, soothing neuropathic pain) beyond the targeted therapy.