Third-party analysis of raw DNA is not as rigorous as that done in a certified laboratory. But many consumers don’t understand that their results are not conclusive.
After two weeks of panic and yet another genetic test at a company with expertise in medical diagnostics, he learned the red box result was wrong. He simply 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 Ancestry.com can say about a consumer’s health.
So many people are taking an additional step: Uploading all the raw data created by these companies to second companies for additional analysis. But these are not firms certified to provide medical diagnoses, nor are they sophisticated academic centers.
Companies like Promethease warn customers not 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.
But it’s not at all clear that consumers understand how uncertain their results may be.
There are no systematic studies of how often the direct-to-consumer results and third-party analyses are wrong. In one small study, Ambry Genetics—a lab certified to do medical testing—looked at 49 samples sent in by physicians whose patients had been told that they had disease-causing mutations by third-party interpreters.
Ambry found that 40% were wrong. In addition, some genetic variations classified by second companies as threatening actually were benign.
This tiny sample doesn’t prove that the false-positive rate is 40%. But patients like 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, director of the Center 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 greatly raises the risk of a number of rare cancers.
Further testing showed that diagnosis was wrong. “It 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 get from a certified clinical laboratory,” said Stephany Tandy-Connor, a genetic counselor at Ambry. “Nothing could be further from the truth.”
Even some doctors are misled by the reports, she said.
Of course, companies like Ambry have an interest in making sure their business is not usurped by consumer testing firms. But it’s also true that the method used by consumer companies is very different from those used by 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 cheap 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 second companies rely on databases that may contain errors—so even if the genetic alteration found by the first company is correct, the analysis can be wrong. Ambry found such patients in its recent analysis.
