How Accurate Is a Dna Test for Medical Readings Permethius
The Online Cistron Exam Finds a Dangerous Mutation. It May Well Be Wrong.
Third-party assay of raw Dna is non as rigorous equally that done in a certified laboratory. But many consumers don't understand that their results are non conclusive.
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Dr. Joshua Clayton, a 29-twelvemonth-old radiology resident at Baylor University Medical Middle in Dallas, wanted to acquire about his ancestry. So he sent a sample of his saliva to 23andMe, the genetic testing company.
His written report was pretty mundane — no new revelations. Merely then he sent the profile created by 23andMe to a split up company called Promethease, which promises to do a more in-depth analysis for genetic mutations that cause disease.
The news was not adept. Dr. Clayton got back a report with a sinister crimson box at the tiptop saying he had a mutation linked to Lynch syndrome, a frightening genetic disorder that leads to potentially mortiferous cancers at an early on age.
In an interview, Dr. Clayton said he "knew, at least cursorily, that false positives were common with these tests." Simply "that didn't alter the frightened feelings or concern, considering I certainly couldn't blow it off."
After two weeks of panic and even so another genetic test at a company with expertise in medical diagnostics, he learned the ruby box result was wrong. He just didn't have the mutation.
More Americans are embracing consumer genetic testing, but the Food and Drug Administration limits what major firms like 23andMe or Beginnings.com can say about a consumer'southward health.
So many people are taking an boosted step: uploading all the raw data created by these companies to second companies for boosted analysis. But these are not firms certified to provide medical diagnoses, nor are they sophisticated academic centers.
Companies like Promethease warn customers non to regard their results as medical diagnoses. Mostly, they are comparing a consumer's raw data to gene variants reported to be linked to disease.
Merely it'due south non at all clear that consumers sympathize how uncertain their results may be.
In that location are no systematic studies of how often the direct-to-consumer results and third-party analyses are wrong. In ane pocket-size written report, Ambry Genetics — a lab certified to practise medical testing — looked at 49 samples sent in past physicians whose patients had been told that they had disease-causing mutations past 3rd-party interpreters.
Ambry institute that xl percent were wrong. In addition, some genetic variations classified past second companies equally threatening actually were beneficial.
This tiny sample doesn't prove that the faux-positive rate is 40 percent. Just patients similar Dr. Clayton are not uncommon, genetic counselors say. And they are increasingly worried about the flip side: false negatives that reassure consumers who actually should be worried.
Dr. Judy Garber, managing director of the Middle for Cancer Genetics and Prevention at the Dana-Farber Cancer Institute in Boston, said one of her patients was told by a consumer testing company she had Li-Fraumeni syndrome, which profoundly raises the risk of a number of rare cancers.
Further testing showed that diagnosis was wrong. "Information technology makes you worry about the people who don't come in," said Dr. Garber.
"People think they are getting the same kind of genetic testing as they would become from a certified clinical laboratory," said Stephany Tandy-Connor, a genetic counselor at Ambry. "Nothing could be further from the truth."
Fifty-fifty some doctors are misled by the reports, she said.
Of course, companies like Ambry have an interest in making sure their business concern is not usurped by consumer testing firms. But information technology's also true that the method used by consumer companies is very different from those used past certified clinical laboratories.
Consumer companies method look for changes in tiny segments of genes, rather than examining the entire gene and looking for alterations. That is inexpensive but not comprehensive.
And because they are not making medical diagnoses, these companies are not subject to the sort of quality controls as certified labs, which require extensive confirmation that results are free of errors.
Compounding the problem, the 2nd companies rely on databases that may contain errors — then even if the genetic alteration constitute by the first company is correct, the analysis can be wrong. Ambry found such patients in its recent assay.
Greg Lennon, a co-founder of Promethease, said that the company'due south reports include a disclaimer proverb the information are "not intended for medical or health purposes." Customers are warned to seek out "an independent, clinically validated exam" if they are told of a mutation and to seek out a genetic advisor.
When errors occur, they unremarkably derive from mistakes in the raw Dna data, said Mike Cariaso, also a co-founder of Promethease.
23andMe offers limited medical testing — for example, looking for iii of the most mutual mutations in breast cancer genes that occur mostly in Ashkenazi Jews. But there are thousands of other alterations in those genes that the company does not track.
The F.D.A. has given 23andMe approval to do similar testing for 10 disorders linked to genetic mutations, simply not for the huge number of others, including Lynch syndrome, that companies similar Promethease wait for.
The variations in Deoxyribonucleic acid in 23andMe'due south raw data "are not for medical or diagnostic use," said Shirley Wu, the company's manager of production science. "The data hasn't undergone the same kind of quality control and validation every bit our variations in our health reports."
The company warns customers of this earlier providing their raw data, Dr. Wu said.
For the consumer who expects validated diagnoses, it's all a flake confusing.
Testing companies like 23andMe say they are non at fault, because they make it clear that their data are not meant to be used for medical diagnoses.
The companies that provide deeper analyses, like Promethease, say they have simply raw genetic profiles created elsewhere and utilise publicly available data to scan for mutations that can increment disease take a chance. Promethease didn't author any of it.
"So much of what I have seen in these D.T.C. tests are false positives and cannot be trusted," said Dr. Robert Nussbaum, principal medical officer at Invitae, a medical testing lab.
Nonetheless, he added, false negatives are even more worrisome.
Dr. Clayton learned only after weeks of agonizing that his Lynch syndrome diagnosis wasn't really a diagnosis at all. "My wife and I were talking about having children," he recalled. "What practice you do? Practice you make that determination to pass this on to them?"
And what nigh disability insurance? If he got cancer, he might non be able to work. But could he even become insurance?
Dr. Clayton searched online for Lynch syndrome experts and found Dr. Theodora Ross, director of the cancer genetics program at the University of Texas Southwestern Medical Center in Dallas.
She had Dr. Clayton'southward Deoxyribonucleic acid tested at a lab certified to make the diagnosis. That was how he institute out the report was incorrect.
He was lucky, he said, that he had medical training and knew where to find aid.
"I don't think that applies to a lot of people," he said.
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Source: https://www.nytimes.com/2018/07/02/health/gene-testing-disease-nyt.html