March 27, 2018 -- Federal regulators are slowly opening a lid on direct-to-consumer genetic testing, allowing people to learn for themselves whether their DNA carries strands that may make them more likely to get some life-threatening diseases.
But whether that lid opens a valuable new toolbox or a medical Pandora ’s Box may depend on what the buyer does with that information, experts say.
Will knowing your cells carry a gene connected to a deadly disease prompt healthy changes, or unnecessary fear? Will a clean report lull people into a false sense of security, leading them to skip steps that might prevent it? How much would you want to know? Who should you tell?
The FDA’s recent decision to allow the popular genetic analysis firm 23andMe to tell consumers whether they carry any of three gene mutations that have been linked to breast and ovarian cancers has brought questions like those to the forefront. Now that it's possible to have more widespread genetic testing, several medical organizations and patient advocates are optimistic, but they also have concerns about unplanned consequences.
“We’re now in an era of rapidly changing science and rapidly changing application of that science, not only to our health care but other aspects of our lives as well,” says Len Lichtenfeld, MD, deputy chief medical officer for the American Cancer Society.
“Inevitably, every time you answer one question … you raise more questions,” he adds.
A Billion-Dollar Industry
Since 1983, when scientists were first able to identify a gene associated with a specific disease, researchers have drawn connections between specific snippets of DNA and dozens of diseases. Genetic testing is already a billion-dollar industry, and some research estimates that it could grow to $10 billion in the next decade. It’s already spawned a new health care specialty: genetic counselors, who help guide people through the process and what their results may mean -- or don’t.
“It’s only going to get bigger,” says Mary Freivogel, a genetic counselor in Denver and former president of the National Society of Genetic Counselors. “Consumers are becoming much more in control of their health care in general. They’re driving health care, and they’re making decisions for themselves.”
But genetic testing “is a very complex area,” Freivogel says. “We need to make sure we have tools in place to guide consumers in the right direction when they’re interpreting what test results mean.”
Advocates say genetic tests can help doctors identify people who are more likely to have some types of cancers or chronic illnesses and recommend steps they can take to manage that risk. A woman who carries the gene variants linked to breast cancer may want to start getting screened earlier and more often -- or even consider preventive surgery to remove all or part of her breasts.
But knowing whether someone has a gene related to a disease is a long way from a diagnosis.
Test Has Serious Limitations
Most genetic testing requires a doctor’s prescription. But the new 23andMe test, which costs about $200, is the only one approved by the FDA for direct-to-consumer genetic testing so far. The mutations it tests for, which happen in genes known as BRCA 1 and 2, are most common in people of Eastern European Jewish ancestry. But the results don’t rule out the presence of any of more than 1,000 other mutations of those genes, the FDA says. And these three mutations included in the 23andMe test are not the most common BRCA1/BRCA2 mutations in the general population.
“We’re still learning what the mutations are,” Lichtenfeld says. “We’re still learning what the mutations mean, and we’re still learning what impact particular mutations may have for a particular individual. Just because it’s there doesn’t mean it’s going to happen.”
It’s the second approval for the company, after an April 2017 decision that allowed it to reveal to buyers whether they carry genes related to 10 other health problems, including degenerative diseases like Alzheimer’s or Parkinson’s. Industry analysts say the market for direct-to-consumer genetic tests could top $300 million within 5 years.
Art Caplan, head of medical ethics at New York University’s medical school, says he was surprised the FDA approved the 23andMe application to test for breast cancer mutations, given the limits of the testing.
“There’s a lot of comment there about how we’re not sure how other mutations affect the ones that are detected here for risk factors, which means the false positives and false negative rate could still be pretty high,” he says. “That means some people might go to drastic action like breast removal but still be a false positive, and other people might relax their guard and engage in riskier lifestyles, but they may be false negatives.”
A false positive happens when testing says you have the mutation in your genes, but you actually don't. A new study found that 40% of direct-to-consumer genetic tests had false positives. And a false negative is when the test says you don't have the mutation, but you do.
Since most breast cancers aren’t caused by the mutations 23andMe can identify, “It seems to me a risk of wasting money on people who aren’t in the risk population,” Caplan says.
In a written response to questions, 23andMe said it “strongly” recommends customers whose results point to a higher risk “to speak to a healthcare professional about additional testing to confirm this result and to better understand their potential cancer risks.”
“This test does not diagnose cancer or any other health conditions and is not a clinical test,” the company says. It doesn’t describe anyone’s overall chances of having a disease, or account for the effect someone’s lifestyle or environment has on that risk.
But the company says a positive test “is very informative and may significantly increase one’s genetic risk for certain cancers, especially breast and ovarian cancer.”
A positive result comes with an e-mail acknowledging that the results “can be upsetting or cause anxiety.” It urges the buyer to discuss the results with a doctor or a genetic counselor for support and “since there may be preventive options that are effective in reducing cancer risk.” The notification also suggests thinking about whether the news should be shared with relatives, “since they may also have the risk variant.”
The approval of the testing is subject to “special controls” to ensure safety and effectiveness, the FDA says -- and 23andMe says it has had to demonstrate its lab’s accuracy to more than 99%.
‘Dozens’ of Options for Genetic Testing
There are now “dozens and dozens” of companies that do genetic testing, says Lisa Schlager, vice president for community affairs and public policy at the breast cancer patient advocacy group Facing Our Risk of Cancer Empowered, or FORCE. But the others require someone getting tested to sit down with a doctor or a genetic counselor to discuss their family history and options first, and can test for more mutations, she says. Some of those tests are in the same price range as 23andMe -- and for women with a history of breast cancer, genetic testing is a covered service under the Affordable Care Act.
“All of that’s missing with the 23andMe test, so it is concerning to us,” she says. And testing only for three BRCA mutations and not others “seems very shortsighted and very limited.”
The risks aren’t just medical. Federal law bars health insurers from denying coverage for people whose genetic makeup suggests they're likely to get a disease, but the same protection doesn’t extend to life insurance, disability, or long-term care policies, Schlager says.
“We believe many people are not prepared for the information they may have up to an 80 percent risk of breast cancer or a 50 percent risk of ovarian cancer,” she says. “They don’t realize the potential implications. They don’t realize they can be denied life insurance.”
And while a false result can be devastating, an accurate finding may be no walk in the park, either.
An Unexpected Answer
In 2009, San Diego resident Jamie Tyrone had her DNA tested as part of a study that looked into whether people whose genes make them more likely to have a disease would change their lifestyles. Though she had a history of Alzheimer’s in her family, she was more concerned about multiple sclerosis.
Instead, she learned she carried two copies of the APOE 4 gene linked to Alzheimer’s -- giving her strong odds that she’ll get the degenerative, currently incurable brain disease. She received the news with no counseling or warning.
“Needless to say, I was not prepared for this information, nor did I welcome it,” says Tyrone, now 57. The news threw her “into a really deep depression,” during which she largely isolated herself.
People with a higher genetic risk of cancer may be able to make changes that can cut their odds of having the disease. “But with Alzheimer’s, there is nothing that’s evidence-based that is proven to prevent or cure Alzheimer’s disease,” she says. “You can change your lifestyle to decrease your risk, but we don’t even know by what percentage you’re decreasing your risk.”
Tyrone is now the founder of a newly launched support group for people who are struggling with their genetic results. She says she’s not opposed to testing, but anyone considering it should have counseling beforehand -- and carefully ponder whether they’re prepared for the results.
“Once that cat’s out of the bag, there’s no going back,” she says.
A Positive Result With a Hopeful Ending
But breast cancer survivor Lara Diamond says a positive result for a BRCA mutation helped her doctor catch her tumor early. Diamond says she got her results from 23andMe in 2013, shortly before the FDA temporarily halted the service -- and she was shocked by the results, since there was no history of the disease in her family and her latest mammogram had been clear.
“First thing Monday morning, I called my doctor, and her response was literally, ‘Oh, crap,’ ” Diamond says. Her doctor recommended a genetic counselor and a second test, which confirmed the 23andMe result. That led to an MRI and the discovery of a roughly quarter-inch tumor. It was removed surgically, with no need for follow-up treatments like chemotherapy.
“My oncologist said that based on the kind of cancer and where it was, we probably wouldn’t have found it for five years, and he said, ‘This conversation would have been very different,’ ” Diamond says.
She doesn’t recommend the 23andMe test for everybody. People with a family history of cancer should get counseling and decide whether to have tests that can check for a broader range of mutations, she says. But she says the procedure should be available: “Let people have the knowledge.”
Is It Worth It?
So is an over-the-counter genetic test for you? Donna Messner, senior vice president of the Maryland-based Center for Medical Technology Policy, said one study of testing for Alzheimer's disease found that after counseling, many people turned it down.
"It’s a different situation for cardiovascular disease or other conditions where there are clear steps you can take to try to head it off," Messner says. "People still need to be counseled on what the genetic information means in those cases, but the implications for intervention are different from a disease like Alzheimer’s."
Caplan says that anyone who wants genetic testing should go to a university or a doctor’s office that has extensive experience and ready advice. But he adds, “If I was really pushed to say what would I spend my $200 on, I would say a health club membership.”
Lichtenfeld says the technology is improving rapidly, and how it’s applied is the subject of a lot of debate in the medical and policy fields.
“There are some who believe in the not-too-distant future, newborns will have their whole genome sequenced, and the information not only about BRCA but many other genetic abnormalities is going to be available at the time of birth,” he says. “I think the implications -- are we ready for that -- is an interesting question to which there is no easy answer.”