Genome sequencing is becoming more common for people diagnosed with cancer. Should it become part of a healthy person’s checkup, too?
A new study published Monday in the Annals of Internal Medicine questions the practicality of making DNA tests standard for people who don’t have a cancer diagnosis or aren’t trying to identify a mysterious disease. While close examination of a person’s DNA might help spot disease early or prevent it altogether, it also might spur “unnecessary costly follow-up,” the authors write.
The study is limited by its small scope, but it is the first with some rigor to examine outcomes when healthy people and their primary care doctors make decisions partly based on a whole genome analysis— that is, a report that shows which of the 6 billion letters in a person’s DNA differ from what might be considered a normal or representative genome (a concept that itself presents problems).
The study is part of the MedSeq Project and comes at a time when the cost of sequencing a person’s entire DNA is about $1,000. The lure of knowing one’s DNA is already big business for ancestry services. Genomics pioneers J. Craig Venter and Leroy “Lee” Hood and others have started businesses to woo customers with health workups that deploy a smorgasbord of tests, include a whole genomic analysis.
Venter’s Human Longevity has begun offering whole genome sequencing to customers and others affiliated with a major life insurance company, which says the tests can “help you and your physician understand your personal risk for disease and how you may respond, or not, to certain medications.”
A private clinic in San Diego, Health Nucleus, which is part of Human Longevity, charges clients $25,000 for a full health workup. Venter said in December that his own tests there caught a previously undetected prostate cancer.
For-profit Arivale spun out of a long-term health project at Lee Hood’s Institute for Systems Biology in Seattle. It provides a battery of tests, as well. Individuals can pay $3,500, and Arivale is working to sign up employees through their employers. It’s aiming for 5,000 customers by the end of the year. Arivale coaches help people interpret their data and, as CEO Clayton Lewis says, their “genetic predisposition”—such as the likelihood of tipping from prediabetes into diabetes. Arivale coaches cannot diagnose disease, says Lewis, but they can lean on scientific evidence to discuss associations between what Lewis calls “lifestyle factors and the potential risk of developing” a disease like diabetes.
While those sequencing healthy people have to skirt around medical claims, the MedSeq study is focusing on medical decisions based strictly on two data sets: Whole genome analysis and a family history report. It randomly shuffled 100 people into two groups: Those who provided their primary doctors with family history, and those who supplemented the family report with an analysis of their whole genome.
The authors, from Harvard University-affiliated Brigham and Women’s Hospital in Boston, Baylor College of Medicine in Houston, and elsewhere, concede that they can only draw limited conclusions because of a small sample size: 50 people were sequenced. But they saw enough in the results to warn about the risk of DNA analysis leading to more medical procedures “of unclear value.”
Eleven of those 50 produced a genetic variant thought to be linked to a disease. But only two of those 11 actually showed outward signs of that disease. One patient had fundus albipunctatus, which impairs vision in low light. The other had variegate porphyria, which causes skin conditions and can also affect digestion and mood. The other nine had no outward signs of the predicted disease, at least within six months of their consultations. Two, for example, had genetic profiles suggesting heart problems, but those problems were not evident after a cardiology exam.
It’s possible that some of the patients could show symptoms later in life, but they were all in their 50s or 60s, says MedSeq author Jason Vassy of Brigham and Women’s Hospital. “We would expect that many of these conditions would have already shown up by now,” he says.
While the participants’ genomic reports often didn’t correlate to other symptoms, the reports seemed to influence doctors’ decisions. MedSeq authors found that primary doctors were more than twice as likely to recommend “new clinical actions” for patients with a family history report and a DNA report (34 percent) than for those who simply presented a family history (16 percent). Those prescriptions led to higher costs. The 11 patients whose sequences detected a potential disease-causing variant averaged $2,526 in costs in the six months after talking with their doctors; the other 39 who were sequenced averaged $1,198.
That said, the small study gave fairly high marks to decisions made by the medical providers. An outside panel reviewed the 11 cases and found eight were managed appropriately. The study also noted that patients’ access to their own genetic data did not seem to produce more anxiety or depression, but more people in that group reported changing their diet or exercise.
Medical providers and insurers are wary of “a wave of unnecessary diagnoses and treatments. We’ve gone through this problem with PSA in the past,” says cancer geneticist Edison Liu, president and CEO of the Jackson Laboratory in Bar Harbor, ME. PSA refers to the prostate-specific antigen screening test, once de rigueur for older men. It was later found to do more potential harm than good and is no longer a routine procedure.
The appropriate frequency of mammography to screen for breast cancer is a matter of debate among different medical organizations and even the U.S. Congress. The risk of unnecessary tests, scans, and surgeries has also colored the current pursuit of a blood test that can screen for early signs of cancer.
With genetic tests, a big problem is knowing whether an abnormality that pops up is a mutation linked to a disease or is a benign variant. “To call a mutation a mutation is a challenge,” says Liu. (His organization is not associated with the MedSeq study, but it is studying the value of tumor DNA testing for community oncologists in Maine who don’t have access to the resources of elite medical centers.)
Vassy says that the field is moving forward because variant databases are linking up, deepening the pool and the understanding of each variant’s disease risk. But perhaps more important, says Vassy, is better interpretation of variants. “It’s still a fairly expert, manual process,” he says. “Those high quality interpretations need to be shared.”
MedSeq will continue to follow the first 100 participants up to five years, says Vassy. The study also aims to be more diverse and is now recruiting a new cohort of African-American participants.