The genomic revolution has the potential to change the practice of medicine and healthcare. Advances in technology are driving down the cost of genetic testing, the public is more aware of and interested in such testing and its uses, and genetic testing companies are now offering direct-to-consumer (DTC) testing via kits sold on the Internet. Some argue that these changes make genetic testing more accessible to the general public and medical community at large and that these changes are critical to the full integration of genomic technology into society. However, many of the DTC tests offered are of questionable accuracy and utility and combine tests that provide mundane information about genetic traits with those for serious genetic conditions with life-threatening implications for the patient and the entire family. We will examine both sides of the issues surrounding DTC genetic testing, focusing on important considerations for clinicians using case vignettes to illustrate key issues.
Is DTC testing worthwhile for your patients?
Point: The testing and result interpretations provided are not necessarily clinically accurate or helpful.
Numerous studies have shown that average patients and clinicians are not well versed on even the most basic elements of genetic testing and result interpretation. 1 It is even less likely that consumers and clinicians will understand the subtle differences between DTC companies and tests—particularly genomic profiling based on single nucleotide polymorphisms (SNPs)—which are offered by most DTC companies. The difference between SNPbased testing and clinical single-gene testing with regard to predictive value is a confusing concept that typical consumers and clinicians without adequate training may not understand. For most of the SNP-based genomic profiles offered DTC, there is a lack of consensus among the scientific and medical communities regarding test interpretation.
The positive and negative predictive values, along with the discriminatory accuracy of these tests, are in sharp contrast to those associated with testing for mutations in high-penetrance Mendelian genes. Discriminatory accuracy refers to the ability of a test to determine who will or will not develop the disease or condition and is a balance between sensitivity and specificity. For example, those who test positive for a mutation in the Huntington's disease gene are certain to develop the disease, whereas those who test negative are unlikely to do so. Similarly, in cancer genetics, those with a mutation in the APC gene (causative of familial adenomatous polyposis) will develop colon polyps and colon cancer without appropriate intervention.
With these Mendelian conditions, the relative risk of disease (penetrance) is large (often 10-fold or greater), and the proportion of disease attribestimated by these companies fail to account for known family history or other risk factors. An investigation in July 2010 by the US General Accounting Office concluded that such tests were “misleading and of little or no practical use.”14 The risk profiles provided by such companies have been described as having “no predictive value” and may falsely alarm or reassure consumers.15
Counterpoint: Individuals have the right to explore their own genetic makeup through these emerging tests and may deem testing worthwhile. Some individuals may learn important information they would otherwise not have learned.
One argument to be made is that genetic technology exists and individuals have the right to explore the testing available, regardless of its accuracy and utility. Many DTC sites do state that their testing is intended for entertainment purposes only, although this statement is often in the fine print (see next point). It is possible that DTC testing has made the public more aware of genetic and genomic testing, therefore encouraging the medical profession to keep up with this technology as it pertains to one's area of expertise. Although some may see this as an additional burden on the primary care provider, it can also be viewed as an opportunity to increase awareness and education on the part of both the consumer and the professional. Most current genomic technology was not developed when most of today’s physicians went to medical school, and even most new graduates are not well versed in genetic testing. DTC genetic testing could encourage the medical community to increase its understanding of this new emerging technology.
Although most of the DTC testing offered is of questionable utility, some panels do include important genetic information, like the three common Jewish BRCA mutations. It may be considered ethically questionable to offer testing for hereditary breast cancer and ovarian cancer without full informed consent and adequate result disclosure. However, one can also argue that individuals will gain potentially lifesaving information they might never have uncovered without such testing.