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What are the dermatologic implications of direct-to-consumer DNA tests?

abstract dna test

23andDermatology

What are the dermatologic implications of direct-to-consumer DNA tests?

abstract dna test

By Emily Margosian, assistant editor

Spit, swab, drop DNA in the mail. Since genetic tests were first offered directly to consumers in 1996, over 12 million Americans have done exactly that. According to the Centers for Disease Control and Prevention, “The concept, then, was both audacious and bold: the idea that individuals could explore their own human genome without the aid of a health care provider.” However, once considered a novelty purchased only by a wealthy few, direct-to-consumer (DTC) genetic tests are now so ubiquitous that they were among last year’s Amazon Black Friday bestsellers.

According to Kavita Sarin, MD, assistant professor of dermatology at Stanford University Medical Center, this surge in popularity is indicative of an ongoing cultural shift. “I think we’re in the middle of two revolutions,” she said. “One — the information revolution, where people realize they can get information on almost anything through the Internet, and now they want it on themselves. The second — the genetic revolution. We now have gene editing capabilities and are technologically able to cheaply sequence human genome and interpret the data that’s found there. I think interest in genetics is only going to grow over the next decade or so.” 

Advertised to help consumers discover genetic insight into ancestry, disease predisposition, and even wine preferences, DTC genetic testing has been both lauded as a potentially democratizing force in public health and criticized as inaccurate and misleading to consumers. As the popularity of at-home genetic tests is unlikely to slow, with an estimated one-third of consumers sharing results with their physicians (J Am Acad Dermatol. 2014; 71(5): 993-995), dermatologists can expect more questions from patients about DTC genetic testing. Likewise, as the cost of genome sequencing continues to decrease in tandem with growing public interest in preventative medicine, consumer demand for accessible genetic assessment is unlikely to slow in the near future.

To help dermatologists navigate this growing trend, Dermatology World consults with physicians, researchers, and medical ethicists to discuss the clinical utility, potential risks, and ethical considerations of DTC genetic testing.

The current market

Although there are many DTC genetic tests currently available that offer ancestry results (even for dogs!), currently there are only two that offer both ancestry and dermatology-adjacent health screening without being ordered by a physician. HomeDNA offers a number of different “themed” tests including weight, allergens, and maternal ancestry. One such offering is the company’s “Skin Care” option, which purports to “take the guesswork out of buying beauty products and unlock your skin’s full potential through genetics.”

The second company is the wildly popular 23andMe, which offers a “Health + Ancestry” package that includes testing for specific genes and carrier status for various diseases. Founded in 2006 by a former Wall Street biotech analyst and named for the 23 pairs of chromosomes in humans, the company rose quickly to the top of the market thanks to initial investments from venture capital and tech-giant Google. Despite suffering a temporary setback in 2013 when the FDA temporarily halted sales of its at-home kits due to concerns about potentially inaccurate results, the company was eventually given the green light to resume sales in 2017. 23andMe has since been authorized to screen for a total of 11 diseases (although it currently only provides testing for nine) and is the first company to garner FDA approval to directly market a genetic test for cancer without a doctor’s orders. With over 10 million customers and counting, the company is poised to continue to grow, having spent roughly $27.9 million on advertising in the first quarter of 2018 alone, as per reporting from NPR.

Practicality: Three questions

While these tests may be fun for consumers, how do they compare to traditional genetic testing? Furthermore, do they have any value for dermatologists when treating patients?

Question #1: Are the tests accurate?

One common criticism of DTC genetic tests is that they lack the clinical utility to support the genetic outcomes and disease-risk associations they reveal to their customers. “Take 23andMe BRCA tests, for example,” said Madison Kilbride, PhD, a fellow in the department of medical ethics and health policy at the University of Pennsylvania. “Currently the test only screens for three BRCA 1 and 2 mutations, despite there being many mutations in those two genes that are known to increase the risk of breast and ovarian cancer. These three mutations are found almost exclusively in individuals of Ashkenazi Jewish descent. So basically, the test isn’t particularly relevant to people from other ethnic backgrounds. An individual who receives a negative result from a test like 23andMe’s BRCA 1 and 2 screen could carry a different BRCA 1 or 2 mutation, or even a mutation in a different cancer susceptibility gene, and still be at risk, but might not understand that as a consumer.”

There can also be variation in risk-prediction algorithms from company to company. In a 2018 study, researchers found that 40% of results sent to patients by a third-party vendor were incorrect or contained false positives, and that some variants classified as threatening were actually benign (Genetics in Medicine. 20(12): 1515-1521).

However, according to Dr. Sarin, the question of DTC genetic tests’ accuracy is ultimately a nuanced one. “The direct-to-consumer market has expanded greatly, and it can range from ancestry and what I would view as mostly entertainment purposes, to cancer susceptibility tests which do give real, relatively reliable information on cancer susceptibility genes,” she said. “I don’t think direct-to-consumer genomics can be lumped as either being reliable or unreliable; it’s actually a large and varied market from direct-to-consumer whole genome sequencing all the way to just genotypic information, which is what a company like 23andMe provides.”

In most cases, however, even if a DTC genetic test does reveal the presence of a variant known to carry increased risk for disease, results are not diagnostic and can’t clearly predict a patient’s chances of actually developing an illness. Likewise, many variants that affect risk remain unknown, further complicating the validity of test results claiming a given level of risk. “When they say that there’s an increased risk of a particular trait or disease, they only have a limited subset of information on a small number of common variants,” explained Dr. Sarin. “While it’s true that those variants might increase the risk of disease, that person may be carrying other variants or mutations that either decrease — or significantly increase — risk of disease. It’s only one piece of the puzzle; it doesn’t provide complete information and is very difficult to base medical decision-making off of.”

Question #2: Cost-wise, how do they compare to doctor-mandated genetic testing?

While the cost of clinical genetic testing can range from under $100 up to several thousand dollars, how do at-home DNA tests compare? DTC genetic tests tend to start as low as $50 and cap around $200. What consumers ultimately receive for their money varies from company to company. Some charge separately for the sample collection kit and subsequent analysis, others may include some form of consultation with a health care provider in the overall cost of testing or as an additional fee. Generally, most health insurance plans do not cover DTC genetic tests — even those that provide information about health disease and risk — because they are done without a referral from a provider and are not considered diagnostic.

Question #3: If a patient brings their results to a dermatologist, are they of any value?

Your patient brings in their test results. What next? According to Dr. Sarin, while the clinical utility of DTC genetic test results is low, they do present the opportunity to provide counseling and a clear perspective to patients. “Patients have definitely started coming in with their 23andMe printouts, saying that they have an increased risk of a particular condition, and it always involves re-educating them that while they do have some variance that has been shown to increase risk, it’s very much just a partial picture,” she said.

Furthermore, the odds of a DTC test tipping off a physician to a serious underlying condition in a patient are quite low. “Their technology is genotyping technology, which for the most part just looks at common variants present throughout the human genome,” explained Dr. Sarin. “Because of that, it is not a platform to detect any rare mutations, only very common variations that predict increased likelihood of traits like blue eyes, red hair, or skin pigmentation. What they can’t do very easily is detect all the BRCA mutations, or BRCA deletions in breast cancer susceptibility, or mutations involved in familial melanoma, because they’re not looking at sequencing for an entire gene.”

Nevertheless, as more patients continue to dip their toes into the world of at-home genetic testing, Dr. Kilbride advises that dermatologists maintain a basic awareness of this evolving market in order to help patients make sense of their results. “While the reality is that all dermatologists can’t be genetic experts, at the same time, given how prevalent direct-to-consumer genetic testing has become in the popular imagination, I think it’s important to have at least a working knowledge of genetics and to be prepared to do some research from time to time,” she said. “Have a sense of what’s out there, and how the tests differ in terms of their clinical significance. The reality is that new tests, including some of questionable quality, are entering the market all the time. Sometimes physicians may just have to say that they aren’t familiar with the test and aren’t comfortable making a medical recommendation in light of the patient’s results. They should still make recommendations for additional testing and referrals to specialists that in their opinion are based on medical need and not just a patient demand.” As such, physicians should find out where to refer their patients with questions about genetic testing (e.g., a local oncologist, a genetic counselor, an academic medical center), recognizing that, in some areas, resources may be limited, she said.

Privacy implications

While direct-to-consumer (DTC) DNA testing can be fun for consumers and exciting for researchers, the practice presents new and potentially troubling privacy concerns.

Potential customers should take an informed approach by asking themselves the following questions before submitting a genetic sample:

Q: How are companies storing my data?

A: Before buying an online genetic test, it’s important to first read the fine print. Most DTC genetic testing companies provide information online about their privacy and security practices. While some of these privacy policies can be unwieldy, consumers should not purchase from a company without first knowing:

  • Who owns your genetic data after you take the test

  • Where your data is stored after submitting a sample

  • How your data is being safeguarded

  • What happens to your genetic information if the company goes out of business

Ideally, companies should offer consumers the option to decide whether or not to store their genetic information after it is analyzed. For example, 23andMe requires customers to sign a “biobanking consent document” to determine whether or not to store their saliva sample. However, the company appears to not have an opt-out for the electronic retention of test users’ results, which leads to...

Q: Can my data be shared or sold?

A: Yes — with a few conditions. In regard to law enforcement, according to the NIH, “Even if a testing service promises not to share your genetic information with others, they may be required by law to disclose the information to authorities in response to a warrant, court order, or other legal requirement.” Famously, this led to the identification and 2018 arrest of the Golden State Killer by matching crime scene DNA with samples obtained from consumer genetic testing databases. Although the killer himself never submitted a genetic sample, authorities were able to pinpoint his identity through a network of relatives who had undergone DTC genetic testing.

Aggregate anonymized genetic data can also be sold by DTC companies for third-party research, although this typically requires explicit consent from the consumer at the time the sample is provided. According to a 2019 NBC News report, data from 23andMe alone has been utilized in more than 110 peer-reviewed studies, with the company having since launched its own therapeutics lab to harness an “ocean-sized” data pool derived from more than four million customers-worth of genetic information.

Q: HOW SECURE IS MY DATA?

A: Only time will tell. In a shifting and often perilous cybersecurity landscape that has made victims of banks, major corporations, political parties, and most recently a major diagnostics lab — consumers may want to think twice about handing over sensitive genetic information without medical necessity. Although most companies claim security practices that involve separately storing customer’s genetic data apart from personal and registration information (such as name, credit card, email, etc.), studies have shown that even aggregated information is not impossible for a skilled hacker to de-anonymize (doi.org/10.1371/journal.pgen.1000167). Additionally, as genetic testing companies continue to sell consumer data to third parties, the risk of sensitive information falling into the wrong hands is likely to increase, and unlike a stolen credit card number, DNA is forever.

ETHICAL CONSIDERATIONS

Whether perceived as empowering tools of personalized medicine or mere medical novelties, DTC genetic tests nevertheless present a unique set of ethical challenges related to their popular use.

One potential criticism is that a positive test result can instill undue anxiety in consumers who are left to interpret findings on their own if a potentially deleterious genetic change is revealed. “It becomes quite complicated when these tests are in the hands of patients who can misinterpret and really change their life after receiving information that’s potentially devastating,” said Amy Paller, MD, chair of the department of dermatology at Northwestern’s Feinberg School of Medicine and director of the Northwestern University Skin Disease Research Center. “Imagine if you’re told you have an increased risk of cancer. Women who are BRCA+ are getting their breasts removed. It is imperative that there be genetic counseling associated with the results. Even results showing potentially pathogenic variants unrelated to cancer risk can cause concern and deserve discussion with a professional.”

According to Dr. Sarin, however, research has yet to show any correlation between DTC genetic testing and increased anxiety in consumers. “Most people who have tried 23andMe have used it to get a big picture of their health and have found it more of a novelty than anything,” she said. “I haven’t really encountered too many patients who have found it anxiety-inducing.” What is problematic to Dr. Sarin, however, is the lack of genetic counseling provided by some DTC genetic testing companies. “One of the problems with 23andMe is that they don’t provide any genetic counseling services, whereas others do provide counseling to discuss the results. I do think that when discussed appropriately it’s fine, but one of the big issues is that there’s just a lack of trained providers, and most physicians aren’t trained to be able to discuss genetic data.”

Dr. Kilbride agrees that the lack of genetic counseling that accompanies the sale of DTC genetic tests poses a serious ethical challenge. “In the clinical setting, you would discuss what the potential results of your test could mean for your health and for your family. With a company like 23andMe, they do recommend that you talk to a genetic counselor and provide links on how to find one in your area, but they don’t actually provide any counseling that could be really important for some consumers,” she said. “Someone might take it for some of the ancestry insight or just for fun to find out more about their earwax or whatnot — and then discover that they carry a cancer mutation.”

DTC genetic testing companies have expanded their advertising reach to specifically market to children. Dr. Paller advises parents to exercise caution before ordering a test for their child. “When we’re talking about children, we’re talking about a lifetime of risk,” she said. “If you’ve got a healthy 70-year-old who finds out he is predisposed to early Alzheimer’s — well, he’s already 70. Imagine finding this in a child. How does that affect lives? There is very little value to them, because so little is actionable. In addition, we know that there are many environmental, genetic, and epigenetic factors that affect the development of disease, so even with a mutation that can cause a disease, there is no certainty about what will happen in the future.”

If parents have true concerns about their children inheriting a potentially harmful condition, Dr. Paller recommends undergoing clinical genetic testing under the supervision of a physician. “If the results show the presence of a deleterious gene that is actionable (i.e., vigorous sun protection and vigilance if a risk of skin cancer), it’s well worth the investigation,” she said. “I say work with a dermatologist and others at an institution to try to specifically look at a gene that runs in the family and get some real information without going through one of these companies. Otherwise, the data may be difficult to interpret and may be upsetting.”

CONCLUSIONS: WHAT’S NEXT?

Where does this leave dermatology and DTC genetic testing? Rather than clinical utility, the true potential of companies like 23andMe may lie in their ability to contribute to academic research, said Dr. Sarin, who has published several studies utilizing aggregate data from the company. “They’ve provided data for large genome-wide association studies for basal cell cancer, squamous cell cancer, and melanoma,” she said. “Their data has been invaluable. Can we use these variants to tell people their exact risk of squamous cell cancer? Not yet. However, it’s a great step forward. The level of information they can provide through crowdsourced data from approximately a million individuals has been extremely powerful.”

On whether or not these tests are good for individual consumers, however, Dr. Kilbride takes a cautious approach. “I think it is complicated. It can certainly be the case that these tests might give people access to information that could be beneficial, but it can also cut the other way where people get information that is difficult to act on or where there aren’t clear-cut medical management recommendations,” she said. “Before I would be comfortable saying whether these kinds of tests are a good or a bad thing, I think we just need more research to understand their impact on consumers.”