Clinicians Should Be Prepared to Discuss Direct-to-Consumer Genetic Testing

By Will Boggs MD

May 01, 2019

NEW YORK (Reuters Health) - Clinicians need to be prepared to discuss the limitations of direct-to-consumer genetic testing and to address the concerns of patients who present with test results.

"The genetic testing offered by companies like 23andMe and most direct-to-consumer testing is not medically useful, and patients should not think they are getting genetic testing that will help with their medical management," Dr. Wendy K. Chung from Columbia University, New York told Reuters Health by email.

In the face of proliferating genetic tests offered by direct-to-consumer companies, the US Food and Drug Administration warned that such testing could threaten individual health and safety and required several companies to discontinue such testing. At present, 23andMe is authorized to market genetic health risk tests for 10 conditions and for 3 specific pathogenic variants in BRCA1/BRCA2.

Dr. Chung and colleagues present a case study in precision medicine and direct-to-consumer genetic testing and discuss how clinicians might respond to patients presenting with direct-to-consumer genetic testing results in their April 30th Annals of Internal Medicine online report.

23andMe does not perform comprehensive testing of all known pathogenic variants, and results may have limited value and sensitivity for patients who are not of European or Ashkenazi Jewish descent.

Moreover, the positive predictive value of many 23andMe genetic tests is limited, because risk is often modified by interacting genes, environment, lifestyle, and family history, which are not included in the risk predictions.

When test results are negative but clinical suspicion remains high, further testing covering all of the genes and variants associated with the condition of concern may be warranted, and the results of such testing should be interpreted and delivered by a provider who is knowledgeable in genetics or by a board-certified genetics professional.

Patients should be told that direct-to-consumer tests are not diagnostic and provide only limited information on disease risk. These discussions should take place in an understandable and culturally sensitive and linguistically sensitive fashion.

"Make sure patients are not misinterpreting the information they are getting back from direct-to-consumer testing, and pursue medically sound clinical genetics testing when there is a relevant question, such as hereditary cancer or carrier screening for reproductive purposes," Dr. Chung said.

"Genetic testing can be quite valuable and when medically appropriate is covered by insurance," she said. "Therefore, make sure patients are getting bona fide clinical genetics testing by a reputable laboratory."

Dr. Lisa Madlensky, program director and genetic counselor at the Family Cancer Genetics Program, Moores UCSD Cancer Center, La Jolla, California, told Reuters Health, "These tests are not a substitute for medical-grade genetic testing. Patients interested in using genetic information for medical care should consider seeking a more comprehensive, medical-grade test in the first place."

"These direct-to-consumer (DTC) tests cover only a small fraction of all mutations in a given gene," she said. "It's similar to spellchecking only three letters out of an entire book. It is not at all what healthcare professionals would consider to be comprehensive testing. That said, DTC testing can sometimes uncover an important finding for a patient, but it still needs to be confirmed in a clinical laboratory."

Dr. Sylvia Metcalfe from Royal Children's Hospital, Parkville, Victoria, Australia, who has extensively researched the use of genetics in clinical practice, told Reuters Health, "Ideally, patients should be counselled about the limitations of undertaking these types of tests before actually buying them. Emphasizing the risk aspect of test results rather than potential for diagnosis is essential, especially as understanding the concepts of penetrance and residual risk are challenging for many people."

"As more companies turn to exome and genome sequencing technologies rather than single nucleotide polymorphism (SNP) arrays, the amount of raw data potentially generated will be staggering, and we simply don't have an understanding yet of the clinical validity of all these variants - the vast majority are variants of unknown or uncertain significance," she said.


Ann Intern Med 2019.