Some patients may soon find out more about their genetic risks than they wanted to — such as whether they are at higher risk for breast cancer or a heart condition — if doctors heed the advice in a long-awaited report issued Thursday.
The report’s authors, led by a Boston medical geneticist, urge doctors who sequence a patient’s full set of genes for any medical reason to also look for two dozen unrelated genetic conditions, and to tell the individual if they find any of those conditions lurking in the DNA.
The recommendation by a national organization of genetics specialists is the first real effort to delineate how broadly testing laboratories should look for, and reveal, additional potential genetic problems — even if the patient is a child. The conditions are only ones in which advance knowledge could be used in prevention or treatment.
Reaction to the report was mixed. Most physicians and bioethicists commended the effort to establish ground rules for how to deal with the vast amount of information in the genome. But they also raised a spectrum of concerns, especially about whether patients should have a choice in what they want to be told about their genes.
“I give them a lot of credit for taking it on,” said George Annas, a bioethicist at Boston University School of Public Health. “Second, I think it needs more work. . . . You can’t just take away patient autonomy.”
The guidelines, approved in a vote late Tuesday afternoon by the board of the American College of Medical Genetics and Genomics, were issued as rapid technology advances have made whole-genome sequencing cheaper and faster. Just a handful of people now have their full genomes sequenced as part of medical care, but many predict that within a few years it will become more common.
Although the recommendations are not binding, they provide important guidance to doctors.
“I’m pretty proud of this, as the first response by an organized medical body to the completely revolutionary aspects of using whole genome sequencing in the practice of medicine,” said Dr. Robert C. Green, a medical geneticist at Brigham and Women’s Hospital and Harvard Medical School. He co-led the group that winnowed the list from 90 genetic conditions to a minimum of 24 that should be searched for in routine testing.
All of the conditions on the list are rare, many of them carrying risk of cancer or heart disease. The specialists who drafted the recommendations estimated that 1 percent of patients undergoing sequencing will have a gene for one of the conditions on the list.
Informing patients they have a gene could help them prevent or treat the disease. For example, a person told he or she carries a gene that causes polyps to grow in the colon and increases risk of colon cancer could get a colonscopy earlier. Knowing they carry a gene that causes extremely high cholesterol could lead people to make lifestyle or diet changes, or take medication to help prevent heart attacks at a young age. Some well-known genes — for example the one that increases risk of developing Alzheimer’s disease — were not included.
The Laboratory for Molecular Medicine of Partners HealthCare has sequenced the DNA of a half-dozen families, and its policy is to prepare a “general genome report” that includes anything of medical relevance, a much longer list than the new recommendations, said its director, Heidi Rehm. So far, patients have had the option to decline secondary findings.
Alan Beggs, director of the Manton Center for Orphan Disease Research at Boston Children’s Hospital, said that as the hospital prepares this year to fully launch genome sequencing as part of clinical care, the recommendations will be taken into account. The guidelines do not apply to sequencing done for research purposes.
The Foye family of Pine Brook, N.J., has seen firsthand how genome sequencing can have unexpected payoffs. They signed up for a genome sequencing study at Children’s Hospital because they hoped to understand the cause of 12-year-old Adam’s rare muscle-weakening disease. Last year, the family got the answer — mutations in a gene called Titin —
In an illustration of how seeking even fairly limited genetic information can ripple outward, understanding Adam’s disease helped his mother, Sarah Foye, receive a diagnosis for an unusual heart rhythm abnormality. The same mutation causing Adam’s disorder caused his mother to have cardiomyopathy, a heart muscle disease that is now being closely monitored. Other members of the family are having their DNA sequenced, to provide information that will help researchers understand Adam’s disease and possibly reveal their own genetic risk for heart disease.
“For me, it did introduce some context of worry, but it gave us an action plan,” Foye said. For Christmas, she and her husband gave each other a membership for 23andMe, a company that provides genomic information directly to consumers.
Dr. Isaac Kohane, chairman of the informatics program at Children’s Hospital, anticipated the problem of sequencing turning up unexpected findings in the genome, and in 2006 coined the term “Incidentalome” to describe the problem. He voiced concerns this week that patients and physicians might be confused about the implications of having some of the genes on the list.
The list includes mutations in two genes, BRCA1 and BRCA2, that dramatically increase risk of breast and ovarian cancer in women with a family history of the disease. The problem, Kohane said, is that the risks such mutations confer are far less well understood in the general population, and the preventive action women could choose to take is extreme: surgery to remove their breasts or ovaries.
“We can actually envisage the following: It’s going to be affordable, almost immediately, if not next year, to get a genome sequence for less than the price of an MRI,” Kohane said. “Does that mean we’re going to have all these BRCA1 mutations now presented to a health care system whose doctors are not well equipped to assess the meaning of those mutations?”
The recommendations also make two major departures from typical practice in medicine and research.
Instead of allowing patients to opt out, telling physicians there are some results they do not want to learn, the recommendations suggest patients be told if they have any of the mutations. Green said it was similar to the way medicine already handles incidental findings. If a radiologist sees a dark spot on an X-ray, for example, the doctor would inform the patient and investigate it further.
The recommendations also specify no age limit for which conditions to identify, meaning that if a genetic risk relevant only in adulthood is found in a child, the parents should be told. Green said the group’s reasoning was that such information could have benefits for the parents or other family members, who might learn of a life-threatening disease risk from a son or daughter.
But ethicists talk of the importance of maintaining an “open future” for children and not using children for parents’ benefit.
The guidelines “go very far in privileging the concerns of the lab and the concerns of the clinician over the rights of individual patients, and the rights of kids to be protected from certain information” until they are old enough to make the decision for themselves, said Susan Wolf, a professor of law and medicine at the University of Minnesota.
Even the team that put together the recommendations said it was far from the final word, suggesting that the list will evolve over time.
“We’re sure we didn’t get it right,” Green said. “We’re sure people will find evidence something shouldn’t be on the list and some things should be. But it’s a starting point.”