The National Cancer Institute hosts a webinar series called Ethical and Regulatory Issues in Cancer Research (ENRICH). This speaker series fosters discussion about ethical and regulatory issues impacting cancer research.
Our CEO/President, Ellen Matloff, was the keynote speaker in the latest webinar titled, “A Scalable Model for Returning Continually Updated Genetic Results to Consumers and Clinicians.” Stream/download the webinar here.
In this webinar, Matloff outlines the ethical principles that must be considered in returning understandable, usable, and current genetic information. She also discusses how to make people stewards of their genetic data by providing them with research opportunities, offering them the ability to provide outcome data, and sharing their genetic data in public databases. She describes how research participants in clinical trials and large-scale genomic studies worldwide, and the 12 million consumers who have had consumer testing, fit into this equation.
Elisha Cooke-Moore’s Tragic Story
- She had a preventive double mastectomy (removal of breasts) and a hysterectomy (removal of uterus) because she was told she had Lynch syndrome based on her genetic test results
- Lynch syndrome is a hereditary cancer syndrome that increases a person’s risk for colon, uterine, ovarian, and other types of cancer
- Her genetic test results were apparently misinterpreted, and she actually carries a variant of uncertain significance (VUS) for Lynch syndrome; this means we don’t know if that genetic change is disease-causing or is completely benign
- She was not offered genetic counseling; no genetic counselors in her area of Oregon; however, genetic counselors are available through phone or video meetings
Misinterpretation of genetic test results is unfortunately common and is becoming more common. Why? Genetics is a rapidly changing field with thousands of genes. Clinicians have on average 12 minutes per patient, including a physical exam. This is not enough time for comprehensive genetic counseling and testing. Clinicians who do order genetic testing are now ordering not just one gene, but panels that include genes that they have never heard of before. This leads to a high rate of misinterpretation. With this incorrect information, patients often pursue inappropriate treatments and/or surgeries.
Test results from laboratories are long and technical but also stagnant. If a patient has genetic testing today and there is an update in the field in a month, year, or decade later, they will most likely not receive that update.
Soon, 60% of the population will be candidates for genetic testing. This includes:
- All pregnant women
- Men and women considering a pregnancy
- Many people diagnosed with cancer
- Many people with personal or family histories of cancer and/or early-onset heart disease
With so many people eligible and pursuing genetic testing, we need more trained health care providers to meet demand. In 2017, the genetic counseling workforce was reported as understaffed by 50%. In an ideal world, we would like all patients to see/speak to a certified genetic counselor, both before and after genetic testing. However, based on the large number of people being tested and the low number of genetic counselors in the workforce, it is not possible. This understaffing of genetic counselors leads to patients receiving inadequate care and errors being made.
Williams vs. Quest/Anthena Case
- Child developed multiple intractable seizures
- Genetic testing was ordered without parents’ knowledge
- VUS was found in SCN1A, a gene linked to Dravet Syndrome
- VUS was interpreted as meaning child did not have Dravet Syndrome; child was treated with sodium channel blocker; contradicted in children with Dravet Syndrome; child died at age 2
- Mother learned of result seven years after test was performed
- Lab reclassified VUS as a pathogenic variant
- For more information about this case read Robert Resta’s piece on The DNA Exchange and GenomeWeb’s coverage
This case points out that variant classification changes over time, and we need to have a way to recontact the ordering clinician and the patients (or parents) when a classification is updated.
Direct-to-consumer (DTC) genetic testing started as “genutainment,” genetic testing people do for entertainment.
Now we know people are getting health information from DTC companies. This includes downloading their raw data and having it interpreted by a third party. But how accurate are these results? Some of the reports can be validated in a medical-grade laboratory and others cannot. Genetic counselor Katie Stoll sent a DTC company a sample containing only tap water. She received a genetic test report signed out by a geneticist “promising to predict the athletic and learning abilities of a child.” Again, this was based on a sample of tap water with no human DNA. For more information on this story, read Katie Stoll’s “DTC: Direct To Children” on The DNA Exchange, where she also addresses the issue of parents submitting their child’s sample for testing without their informed consent.
We as health care providers need to learn how to deal with these findings, discuss them with patients, and repeat them in a medical-grade laboratory. If confirmed, we need to incorporate them into medical care.
What are the underlying principles, ethics, and tenants of genetic testing?
Consumers who choose any type of genetic testing should be able to receive their genetic data, share their genetic data if they choose (some companies do not allow this), and understand and use their genetic data.
Which group of test results are the most overlooked? Negative test results in the context of a strong personal and/or family history. These cases are often the most challenging cases, yet the least likely to receive genetic counseling. Patients in this group are often presumed to be at an average or low-risk, which is very dangerous in the context of having a personal and/or family history of a disease.
Ideally, the source of patients/consumers receiving genetic information should be from an unbiased third party who is:
- Not selling genetic testing
- Not selling drugs, supplements, and/or vitamins
- Providing the risks, benefits, and limitations
What are the aspects of an ideal return of genetic test results?
- Digital genetic counseling information for every patient/consumer having genetic testing
- Device agnostic and easy to use
- Can be revisited any time and over time
We are moving into a new era of health care in which the consumer and family must be central to this information and process.
Information should be linked by gene and variant because genotype phenotype correlations will become more common in the future, and we need a way to recontact subsets of patients. This information needs to be updated with new studies. As new data unfold, clinicians and patients should be alerted via email or text. Referrals to a certified genetic counselor should be offered for those who need or want it.
The Golden State Killer was caught through genetic testing. This is a landmark case because the criminal was identified by matching his DNA, which was isolated from a sample he left in a public place, to a genealogy testing bank.
This opens the discussion for all the potential ways public sharing of family trees and DNA samples could be used in ways in which consumers have never consented or imagined. It is clear we need to give a lot of thought to this.
All of Us Study
The All of Us study, which is recruiting a million participants, is another reason we need to consider how we will protect data, make participants feel safe, and allow everyone to understand the testing and results. These are among the major challenges ahead of us in genetic testing.
For more information about NCI’s ENRICH Forum, including past and future webinars, please visit their website.