Should patients be told of unexpected risk factors lurking in their DNA?

When a national organization of genetic specialists took a stab at clarifying one of the biggest issues facing the integration of DNA sequencing into medicine in March, the bold guidelines seemed destined to stir up a hornet’s nest of controversy.

The recommendations suggested that patients who have their genomes sequenced should be told of select incidental findings—genetic risk factors for conditions unrelated to the reason they got their DNA sequenced in the first place. In a major departure from current norms in the nascent field of genome sequencing, the group said patients should not have a choice about which risks they wanted to know. And risks for diseases that do not strike until adulthood were also to be disclosed to children’s parents, counter to the longstanding idea that it is important to preserve an “open future”—meaning doctors should wait until the patients are old enough to decide for themselves whether they would like to know their risk of breast cancer, for example.

Now, the response—call it a backlash, call it a healthy debate—has begun, even as the guidelines begin to have an impact on the kind of testing being offered to patients. A critique was published last week in the journal Trends in Biotechnology. Meanwhile, two companies have announced they are adopting the guidelines, though with an opt-out provision.

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Dr. Robert C. Green, a medical geneticist at Harvard Medical School and Brigham and Women's Hospital

Dr. Robert C. Green, a medical geneticist at Brigham and Women’s Hospital who co-led the working group that drafted the recommendations adopted by the American College of Medical Genetics and Genomics, said that he expected a vigorous public discussion about the guidelines and thinks the debate will benefit the field. But he added that he is surprised at how quickly things are already moving forward.

“Some of the recommendations from professional organizations have taken 10 years to actually start being practiced,” Green said. In this case, within weeks, two commercial labs announced they would integrate the new panel of genetic risk factors into their sequencing tests, which include mutations that cause rare heart problems or cancers. All of the conditions on the list are for serious illnesses that are clinically useful, meaning that patients can take measures to prevent disease, detect it early, or decrease their risk.

Even though the companies have decided to allow patients to decline to learn the information, Green said it was a fantastic start.

“I think as clinicians order this, they may see that it’s not troubling the patients who opt in—and they maybe discover some lifesaving information,” Green said. “I think it will reassure the field.”

As of May 1, GeneDx announced that it will integrate the panel of gene mutations into some of its tests, although it would allow patients to decline receiving the information. A second company, Ambry Genetics, is also integrating the panel of genes associated with the two dozen conditions into its sequencing results, and will allow patients to opt out.

The opt-out provision reflects a main component of the critique published last week by two ethicists from Stanford University School of Medicine, which asserts that saying patient wishes not to learn certain genetic information “should be over-ridden by physicians for the patient’s ‘own good’ is weakly supported in modern clinical ethics.”

The Stanford ethicists also question the reasoning of Green’s working group, which suggested that it would be expensive and logistically onerous for laboratories and genetic counselors to implement the extra testing only conditionally, depending on the patient’s desire.

Because the list of conditions that should be searched for and disclosed is expected to expand, the ethicists argue that a growing host of conditions may become mandatory information for anyone who gets their genome tested. To the ethicists, that sounds similar to population-based screening, such as a recommendation that all women above a certain age receive mammograms, which typically requires much greater evidence of the risks and benefits.

Green, however, disagrees. He sees the argument that genomic information should be withheld from patients as paternalistic, hearkening back to a time when doctors might have withheld from a person the fact that they had cancer or another terminal disease. While the information in the genome vastly increases the amount of potentially incidental, health-related information that could be learned compared with a physical exam or other type of test, he notes that this is the type of “opportunistic screening” that occurs every day in doctor’s offices around the country. A physician examining someone for a skin rash would not willfully ignore a mole that shows the tell-tale signs of melanoma just because it is not the reason the patient came in.

“It is a type of screening that occurs every day in almost every branch or practice of medicine,” Green said. Patients “don’t expect us to put sticky notes over the part of the X-ray that isn’t pertaining to the reason they got it.”