Your patient, a 55-year-old woman with estrogen receptor-positive, progesterone receptor-positive, HER2-negative breast cancer, says she is thinking about doing direct-to-consumer genetic testing (DTCGT) to see whether her children are at increased risk for developing breast cancer. How should you respond? Later that day, your 35-year-old neighbor, who is a mother of 2 children, stops you and asks which online genetic testing company you think is best. What should you tell her?

DTCGT is now a reality, and oncology nurses are going to get more and more questions from patients about what it is and whether they should do it. We have a responsibility to educate these patients and their families about it.

There are a number of factors to consider when discussing DTCGT with a person who has breast cancer. Before you respond, more information is needed. What is her family history: Is it suggestive of hereditary risk? Is she worried about hereditary risk? Does she know the strengths, limitations, and risks of genetic testing? Does she understand the possible range of results that might be reported?

DTCGT is not likely to accurately clarify genetic risk for developing cancer in your patient and neighbor or their families. If family history is not suggestive of hereditary risk, there is an opportunity to provide education about what DTCGT will or will not do. Oncology nurses have a professional responsibility to identify patients who may have hereditary predisposition to developing cancer and assure that they get referred to appropriate resources and professionals who can guide them through risk assessment and the genetic testing process when it is appropriate.

FACTS ABOUT DIRECT-TO-CONSUMER GENETIC TESTING

Until 2006, only healthcare professionals could order genetic testing. Then 23andMe launched at-home genetic testing.

 DTCGT is marketed straight to consumers through television, print advertisements, and the internet, including social media. This form of testing provides limited access to an individual’s genetic information without necessarily involving a healthcare provider. Typically the individual reads about the test online, orders the desired test, pays by credit card, receives a kit by mail, obtains a saliva sample, mails the test back to the laboratory, and receives results usually online through a password- protected account. The apparent simplicity and relative low cost (approximately $100-$250) make it attractive.

Risk for developing various diseases can also be discerned through DTCGT. This has been a controversial area. The original 23andMe kit provided tests for the 3 BRCA founder mutations. In 2013, the FDA pulled the health risk testing in the 23andMe kit, limiting the test to ancestral information and some traits.

 In April 2017, the agency agreed to allow 23andMe to add back to the test kits its limited genetic testing for about 10 medical conditions, including Parkinson disease and late-onset Alzheimer disease.

At that time, the FDA planned to exempt other 23andMe genetic health risk tests from premarket review. Further, it indicated that companies offering similar tests might be able to forgo intensive regulatory review after submitting the first premarket plan.4 In March 2018, 23andMe added the 3 founder BRCA mutations back to the test, opening the door to add other health risk tests without additional market review.

DTCGT can also include testing for a variety of other human traits.

These might include alcohol flush reaction, caffeine consumption, earwax type, deep sleep patterns, genetic weight, lactose intolerance, muscle composition, sleep movement, and presence of a unibrow. Trait reports are based on the presence of one or more combinations of single-nucleotide polymorphisms (genetic variations that represent a difference in a single nucleotide in the DNA); the clinical utility or usefulness of this information is often very limited.

DTCGT is big business, accounting for an estimated $230 million in business annually.

 Regulatory oversight is confusing, however. In the United States, the Clinical Laboratory Improvement Amendments of 1988 require that laboratories providing DTCGT results to the public are certified and employ certain basic practices, although there is no assurance that the DTCGT will offer clinical validity or utility. The only oversight by the FDA on testing for genetic diseases is in the regulation of test kits marketed and sold to labs for use in testing procedures. The Federal Trade Commission is responsible for assuring that advertising about DTCGT is honest and not misleading.

Oncology nurses need to ascertain whether the personal and family histories are suggestive of hereditary risk. For individuals with early-age- onset cancer or multiple family members with a diagnosis of cancer, referral to a genetics professional is the appropriate next step. DTCGT is not likely to provide accurate or comprehensive information about hereditary risk for developing malignancy. Interpreting results can be challenging, especially when a knowledgeable healthcare provider is not readily available to explain the results and the implications for other family members.

Prior to engaging in genetic testing, individuals should have enough information to make an informed decision. Informed consent may be difficult to obtain from the fine print on the company’s website. Individuals need to realize there are no protections for life, long-term care, or disability insurance and that these limitations should be considered and addressed prior to testing. Individuals engaging in DTCGT need to realize that the company may sell and use the DNA it collects for other research or commercial endeavors.

DTCGT is not going away. It will likely become more prevalent and more complex. Patients, their families, and neighbors are going to casually remark that they engaged in DTCGT or ask about it. Oncology nurses need to be prepared and proactively and accurately address concerns about genetic testing.

, is Professor, Division of Hematology/Oncology, Department of Internal Medicine, and Professor, Adult Nursing, School of Nursing, Saint Louis University. 

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Articles

Mail-in DNA tests may not provide enough information to people looking for answers about their genetic predisposition to cancer.

How to Advise Patients About Direct-to-Consumer Genetic Testing

Direct-to-consumer genetic testing (DTCGT) can offer information about ancestry; risk for developing some diseases including cancer, heart disease, malignancy, and Alzheimer’s disease; and physical traits. Different companies offer different options and combinations. But there are unintended risks that can come along with genetic testing.

Oncology nurses may have questions from patients and families about the significance of ancestry testing and how it is done. Although individuals may think ancestry testing is fun and entertaining, they may not realize there are hidden risks. For those undergoing the ancestry testing, there is a risk that an individual may learn that they are not related to persons they initially believed to be their biological family. The emotional consequences can be significant.

Conversely, individuals could learn they have other close relatives that they were unaware of or had been separated from, and may not want to know such information or be prepared to learn about it. Credentialed genetics professionals routinely discuss this possibility in pretest counseling so individuals realize it is a possibility.

Many are intrigued by DTCGT because they hope to better understand their ancestral roots which is often referred to as genetic genealogy. Three types of genetic ancestry testing are commonly used for genetic genealogy

Y chromosome testing: The Y chromosome is passed exclusively from father to son, and can be used to explore ancestry in the direct male line so it can only be done on males. Females who are interested in this type of genetic testing sometimes get a male relative to have the test done to add this information to the ancestry assessment.

Mitochondrial DNA: Mitochondrial DNA testing is helpful for understanding female lineage. Although most DNA is contained in chromosomes within the cell nucleus, the mitochondria also have a small amount of DNA. Males and females have mitochondrial DNA, which is passed from their mothers, so this type of testing can be used by either males or females to provide information about maternal lineage.

Single-nucleotide polymorphisms (SNPs): SNPs are genetic variations that represent a difference in a single nucleotide in the DNA. Each SNP represents a difference in a single nucleotide which is a building block in a strand of DNA. SNPs occur regularly in every human’s DNA with an estimated 10 million SNPs in the human genome.

 In many cases SNPs play no role in gene function but some are found in a regulatory region of a gene where they may play a more direct role in disease by affecting the gene’s function. SNPs can be compared across a person’s entire genome. The results are compared with those of others who have taken the tests to provide an estimate of a person's ethnic background. Genealogists use this type of test because Y chromosome and mitochondrial DNA test results, which represent only single ancestral lines, do not capture the overall ethnic background of an individual.

Most DTCGT that offer testing for predisposition to developing disease and ancestry testing only look at  some SNPs. It is not sequencing of an entire gene and not sequencing of the entire human genome.  For example, 23andMe offers genetic testing for the 3 founder mutations in the BRCA1/2 genes found in approximately one in 40 persons of Ashkenazi Jewish ancestry.

 It does not offer complete sequencing of the entire BRCA1/2 genes for the more than 1,000 known mutations or any of the other genes associated with an increased risk for developing breast and/or ovarian and other cancers for which genetic testing is readily available. SNPs can be analyzed to assess predisposition and in various combinations are also utilized to evaluate ancestry.  By combining information from the Y chromosome testing when available, mitochondrial DNA, and selected SNPs it is possible to estimate ancestral roots and sometimes identify close relatives.  The more cases in the database, the greater the chance of identifying another relative.  Persons doing DTCGT need to understand that their data is being utilized for this purpose as well as other research purposes.

There can be surprises with genetic testing. The focus of pretest counseling with a genetics professional is to provide enough information that the patient can make an informed decision and to explain the possible range of results. DTCGT is not comprehensive genetic testing so a negative test result on an SNP for developing cancer is noninformative. Individuals need to realize they could have a test result that suggests they are at high risk for developing a disease, such as Alzheimer’s, and that there is no prevention strategy for the disease, which could result in worry.

Those doing ancestry testing could also learn about misattributed paternity or maternity or that they have another close relative which can be emotionally disturbing.  In the case of misattributed paternity or maternity, an individual might also learn they are at increased risk for developing other health conditions such as malignancy which can be very distressing.  In cases of adoption or the potential misattributed parents, credentialed genetics professionals alert patients to the possibility and potential management strategies.  In cases of adoption, genetic counselors discuss notifying the agency in the case of a positive test result so other family members potentially at risk have the option of testing. With DTCGT, this potential ethical issue is usually not discussed. In the case of comprehensive cancer genetic testing, credentialed genetics professionals emphasize that results have implications for an entire family, as well as the importance of sharing results. This can be challenging and stressful for some families. It is much more difficult when an individual unexpectedly learns that their family is not who they thought it was.

When patients and friends express an interest in DTCGT oncology nurses have an opportunity to educate on the science behind DTCGT as well as what individual might learn or not learn from DTCGT.

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Genetic testing for cancer may result in unforeseen revelations.

Surprise, You Are Adopted

Proponents of direct-to-consumer genetic testing (DTCGT) acknowledge that it enables individuals to pursue testing independently and without interference from a healthcare professional.

Genetic testing may help people better understand health risks and motivate them to engage in a healthier lifestyle.

 Another possible benefit is that they have some control over privacy and whether or not the information will be placed in their medical records.

 DTCGT may also raise public awareness of the importance and role of genetic testing in healthcare.

DTCGT is not comprehensive genetic testing.

 In fact, the new 23andMe test only tests for 3 mutations on the 

 genes for which there are well over 1,000 known mutations. It does not test for the many other genes associated with increased risk for developing breast cancer. It is not even close to comprehensive genetic testing, and consumers may or may not understand this.

Consumers are at risk for being misled by the results of unproven or invalid tests as well as tests that have limited clinical utility. Without guidance from a healthcare provider, they may make important decisions about treatment or prevention based on inaccurate, incomplete, or misunderstood information about their health. For example, a woman who tests negative for the 3 founder 

 mutations may mistakenly conclude she does not have elevated risk for developing cancer when she actually harbors another breast cancer susceptibility gene that has implications for her health and healthcare as well as that of her siblings, offspring, and other relatives.

Conversely, the individual who has undergone testing may engage in inappropriate and potentially harmful health-related behaviors if the risk is overestimated. Genetic testing provides only one piece of information about a person’s health—other genetic and environmental factors, lifestyle choices, and family medical history also affect a person’s risk of developing many disorders. These factors are discussed during a consultation with a doctor or genetic counselor, but in many cases are not addressed by DTCGT.

Psychosocial distress for the individual and the family following DTCGT is another concern. Without genetic counseling prior to genetic testing, an individual may not be emotionally ready to learn that they have increased risk for developing a disease for which there may or may not be a means to decrease or mitigate the risk and can be associated with an increase in distress.

In DTCGT, true informed consent may not be possible because the risks and limitations of testing are often described in the fine print and in footnotes on the website.

A content analysis of 23 health-related DTCGT websites found that information about the benefits of the testing outweighed information about its risks and limitations by a ratio of 6 benefits to 1 risk or potential limitation of testing.

 Also, buried in the fine print is information about how the genetic testing company can use data, often to their financial advantage, without further compensation to the consumer. Fine print may include information that data may be shared with research partners, including commercial partners or perpetual, royalty-free, worldwide, transferable license to utilize the extracted DNA for other research.

An important component of pretest genetic counseling with a credentialed genetics professional is a discussion of the risks and possibilities of discrimination with genetic testing. Although there are federal protections against discrimination for employment and health insurance through the Genetic Information Nondiscrimination Act (GINA), individuals undergoing DTCGT might not fully understand the risks for trying to obtain more life, long-term care, or disability insurance.

 During pretest genetics counseling, credentialed genetics providers carefully review this information.

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Direct-to-consumer genetic testing enables individuals to pursue testing independently and without interference from a healthcare professional. But is there a downside?

Suzanne M. Mahon RN, DNSc, AOCN, AGN-BC

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