You Want to Do What? My Mother's Choice to Have ...

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Given the way in which my mom embraces technology, I should not have been ... about esophageal cancer based on his 23andMe results. The geneticist had ...

J Genet Counsel DOI 10.1007/s10897-012-9482-1

PROFESSIONAL ISSUES

You Want to Do What? My Mother’s Choice to Have Direct-to-Consumer Genetic Testing Elizabeth A. Varga

Received: 27 July 2011 / Accepted: 6 January 2012 # National Society of Genetic Counselors, Inc. 2012

Abstract As a genetic counselor, I had mixed opinions when my mother told me of her intent to undergo genomewide, SNP-based direct-to-consumer (DTC) genetic testing. I cautioned her that results could be misleading, could increase anxiety and were often of limited clinical validity or utility. I warned of the possibility of learning unintended health information and expressed concerns about how the information might be used by a private company. I told her about the variability in results among companies. Yet, she persisted in her desire, reminding me that she was an informed consumer. After reviewing her goals and understanding of the information she might receive, she elected to proceed. Despite my insistence that I would not be her personal genetic counselor, when the results came back, I found myself immersed in her genetic data. In this manuscript, I will examine how this personal experience challenged my perceptions of DTC testing. Keywords 23andMe . Direct to consumer genetic testing . Genetic counseling

My mom is a source of inspiration to me. She has an insatiable appetite for learning and always challenges herself in new ways. As an elementary school science teacher, she

E. A. Varga Division of Hematology/Oncology/BMT, Nationwide Children’s Hospital, The Ohio State University, Columbus, OH, USA E. A. Varga (*) Nationwide Children’s Hospital, 700 Children’s Dr., ED5GG, Columbus, OH 43205, USA e-mail: [email protected]

made just about everything into an “experiment” and instilled a love of biology in me early on. Given the way in which my mom embraces technology, I should not have been surprised when she called to tell me that she was thinking about undergoing genomewide SNP testing through 23andMe. She wanted my opinion on whether or not I thought she should do it. Her call came just three days after one of our geneticists had presented a case in clinical conference about a man concerned about esophageal cancer based on his 23andMe results. The geneticist had emphasized how the result was very misleading because the study referenced in the interpretation was based on a population of 6,000 Chinese men and his patient was Caucasian. We discussed how the reference population was not appropriate for generating a risk estimate for this patient, and the data were too limited to draw firm conclusions. Given this context, and the fact that I had read articles on the inconsistencies among different DTC companies’ interpretations on the same disease (Kutz 2010; Kuehn 2010), I was not very “sold” on the idea of my mom undergoing this testing. I explained to my mom the limited clinical utility and predictive value of this testing, as well as the importance of gene-environment interactions in determining phenotype (Palomaki et al. 2010). We discussed the genetic information that could be revealed (e.g. an increased risk for a disease like Alzheimer’s or a BRCA mutation) and the fact that some things may not be preventable. I tried to ascertain what my mom hoped to learn from the information and explored how she thought she might react to negative news. We also discussed the possibility of false reassurance (Salkovskis and Rimes 1997). I expressed concerns about how the information might be used for proprietary purposes, since there are no uniform standards regarding the use of samples or information by private companies (Reis 2010). Despite my best efforts to dissuade her, my mom decided to proceed with

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testing. She reassured me that she was not the typical consumer– she had a good understanding of the science and statistics, was a decent skeptic, and was mostly seeking entertainment and amusement. I cautioned that I did not want to be her personal genetic counselor when the results came back. This was in part because I did not want the daunting task of going through each piece of data and providing an independent interpretation. On a more personal level, I was concerned about my ability to counsel my mother objectively. Finally, I feared learning anything that might have implications for my own health, especially since I was pregnant and already having a lot of anxiety. A few short weeks later, the results arrived in my mother’s inbox. On the night they were received, my mom and I were talking on the phone. She made the statement, “By the way, you have nothing to worry about. My 23andMe results came back and confirmed what I already knew. The results confirmed disease risk for conditions I’ve either already developed or have known that I was at risk of developing. For many things, I was very reassured. For one thing, I now know that I am not a carrier for several diseases.” With knowledge that, on a superficial level, the results seemed benign, my curiosity set in. I began asking more questions and before I knew it my mom said “I am just going to share my report with you using a link; that way you can take a look yourself.” Despite my own misgivings, my compulsivity took hold and that night I found myself immersed in my mom’s genetic data. To my surprise, I was very intrigued and also impressed by the wealth of information that was provided. I was struck by how basic the overview report appeared; it simply laid out the increased or decreased probability of different diseases or traits. However, by clicking on each disease, I could obtain great detail. For each disease, the SNPs tested and resulting genotypes were provided, along with scientific journal references and a lay summary about each study describing the population, sample size and strength of association. In some cases, a copy of the lab report explaining the test methodology, sensitivity and specificity was accessible. There were graphical depictions to illustrate absolute and relative risks. There were charts showing how much of the disease is thought to be due to heritable and non-heritable factors. For those with a less scientific background, there were animated videos explaining basic genetic concepts along with a glossary of terms. I found it comforting to see genetic counseling recommended on almost every page, along with other resources such as support organizations and disease-specific websites. There were practical tips on things that one can do to lower disease risk and many seemed reasonable and appropriate. As my mom had said, she learned some things that she already knew or expected. She had been previously diagnosed

with factor V Leiden and that was confirmed through analysis of the G1691A polymorphism (SNP rs6025). But unlike when she was actually diagnosed with factor V Leiden in 1998, 23andMe provided a full report explaining what it is, the associated disease risks, and information about prevention, support and genetic counseling. There was an interview with a physician that provided a balanced discussion of the implications of finding this mutation, the importance of family history and other tests that might be recommended. I found myself wishing our family had been given such comprehensive information at the original diagnosis; we were given little at the time and were left largely to our own devices to figure out the implications. Many of our relatives had frustrating experiences with doctors who were uninformed, or even ordered the wrong test. In our family, this direct-to-consumer test would have been appealing due to accessibility, cost, and confidentiality, since many were concerned about life insurance discrimination. 23andMe predicted my mom had an increased risk of ulcerative colitis, with a relative risk of 1.4 and absolute risk of 0.7/100. My mom has already been diagnosed and treated for this condition. Both of us were surprised that her risk did not come out higher. Further examination of her report revealed that only 4 SNPs were tested, each accounting for a very small proportion of heritable risk. 23andMe also estimates the heritability of ulcerative colitis at 50-60%. My mom’s physicians have always speculated that stress and other environmental triggers played a significant role in her disease, so her results made sense to her given this context. The most surprising and disconcerting result for my mom was her increased risk of coronary artery disease, quoted as a relative risk of 1.6 and an absolute risk of 39.6%. We always worry about cancer in my family, given that this disease has affected and eventually killed both of my mother’s parents and their siblings. Therefore, heart disease is not high on our radar. It probably should be considering my mom is treated for hypertension, has tachycardia and a history of transient ischemic attacks. Her brother also recently had a myocardial infarction at 57. Examining the report in more detail, my mom has an allele related to increased lipoprotein(a) production and another involved with triglyceride levels; together these 2 alleles seemed to have the most impact on her combined risk estimate. My mom has had elevated triglycerides in the past, though she was unsure about Lp(a) levels. She put this on her list to discuss with her cardiologist and was glad to have a reminder that she should pay attention to her heart health. My mom learned some things that were just for fun—for example, she is a fast caffeine metabolizer. I could have guessed that considering she drinks 4-6 cups of coffee a day, including one just before bed. We also learned that she is

Mother’s Choice to Have DTC Genetic Testing

prone to nausea and vomiting post-op; interesting, that might explain why I had a similar reaction? My mom found it comforting to know that she screened negative for common mutations associated with over 20 different autosomal recessive diseases, including Canavan disease and sickle cell anemia. As a genetic counselor, I recognized that based on ethnicity she was at low risk to be a carrier for many of these diseases. In addition, the screen only included the most common associated SNPs, often unique to certain ethnic groups. However, in some cases, the SNPs tested accounted for a large proportion of the disease-associated risk alleles. As I explored them in detail, I was impressed with how comprehensive the technical reports were. They provided information about the percentage of disease risk accounted for by the tested SNPs and described the limitations. Certainly the panels used for some of the diseases were less inclusive than those we may offer in a clinical setting, but for someone with a low baseline risk, this provided more information than would be typically offered. For example, I have been tested for cystic fibrosis and spinal muscular atrophy as part of my preconception screening, but had no information about connexin-26 or other conditions. Although not complete, I found some reassurance having a few additional pieces about my family DNA. Of less interest to my mom, but of significant interest to me, was the “research” section of the site. Consumers can fill out questionnaires about all kinds of traits, ranging from detailed medical history to information about personality. If one has been previously diagnosed with a condition of research interest to the company (which are clearly identified on the website), a more in-depth enrollment process and questionnaire is involved. Before completing these, users are reminded of the company’s privacy, “honesty and transparency” and terms of service policies. After reviewing the information, one provides consent with a checkbox; definitely not the informed consent process I am used to as a research coordinator. 23andMe’s research findings, which include newly reported gene-disease associations or replications of previously published data, are advertised on their website in the form of press release-style articles or links to scientific manuscripts that they have published in peer-reviewed journals. Despite approximately 4 hours of exploration, I have only examined a small portion of the results available to my mother. I have learned a lot along the way, not only about the technology, but also the testing experience from my mother’s, and my own, point of view. First, I was impressed by the volume of information that can be obtained through this testing process. Some of it was helpful (i.e. the summary on venous thromboembolism and factor V Leiden which was so well-written and comprehensive that I wanted to immediately copy and share with friends and

relatives). Some of the information was entertaining, but of little practical use (i.e. we already know my mom has blue eyes). Most of the information probably has little clinical utility and further research needs to be done before drawing firm conclusions. Despite the limitations, my mom and I both felt that some information was better than none, and we felt that the company did a good job trying to put the information into some context and educate the consumer. Neither of us felt that the information was harmful or anxiety provoking in any way, similar to others (Bloss et al. 2011), though we recognize others may have differing experiences. These findings will not likely lead to any significant behavioral changes either, but at the outset of testing, my mother did not intend to use the results for that purpose. In thinking about the world of direct-to-consumer testing, there are obviously advantages and disadvantages. The disadvantages are many and include (but are not limited to) the risks of learning unintended information, being falsely alarmed or reassured, or having your personal genetic data used for proprietary purposes. Some of these risks may be understood by consumers, while others may not. Furthermore, there is no question that the information presented is complex and requires high health literacy to interpret. It is also of limited value given that family history or environmental risk information is not incorporated. Certainly the online consent process is more limited than the traditional informed consent process. Finally, it is alarming to me that samples from adolescents and children can be submitted, creating potential harm of labeling and removing the child’s autonomy. On the other hand, there may be advantages to direct-toconsumer testing. One obvious advantage is to promote interest in and awareness of genetics, and improve familiarity with genetic concepts and terminology among the public. Having “personalized” results definitely made my mom ask more questions about genetic associations with disease and gave her the incentive to learn more about it. It was exciting to hear my mom, and see other members of the lay pubic online, communicate about SNPs and haplotypes. It is also apparent that 23andMe, and possibly other companies, are acquiring volumes of genetic and selfreported phenotypic information from their participants. As a researcher, I see the potential this may have to increase the pace of genetic discovery through the recruitment of large cohorts of individuals. Although I am excited about the potential opportunities this may bring, my concerns about the consent process and use of information for proprietary purposes remain. DTC testing also improves access to genetic information and allows for an individual to obtain test results confidentially. This may be an advantage in some cases, as exemplified in my own family where my relatives were well-educated about the implications of factor V Leiden, but had limited

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access to testing and were concerned about risks of insurance discrimination. After this experience, many people have asked me if I would have DTC testing or recommend it to my patients. Thus far, I have not undergone testing, because I do not have the same desire to delve into my genome like my mother did. I also view much of the information provided to be experimental with limited clinical utility. Similarly, at this time, I would not recommend this testing to my patients. This is because as a medical professional, I have the responsibility of identifying the most accurate and appropriate testing, while minimizing harm. In the majority of cases, this will require a targeted clinical test that can be interpreted by a health professional in the context of personal and family history. In sum, as genetic counselors analyzing DTC technology, I think it is important to be educated about the limitations, including real concerns about clinical validity, utility, privacy and regulation. There is wide variability between companies and all DTC tests and interpretations are not created equal. I think it is important to voice our concerns to patients and the public, and to be advocates so that these are addressed. However, I also believe we should recognize potential benefits of this technology and appreciate the elements of the testing and education process that are done well. We should not underestimate the opportunities this technology provides to increase genetic literacy among the public, enhance scientific discovery, and improve our individual and societal knowledge about the relationships between genetics and disease.

Acknowledgement I would like to thank my mother, Kathleen Reed, for sharing her testing experiences with me and others. You can read her personal reflections on her testing experience on http:// jonesfamilymatters.blogspot.com/ entries dated June 13–20, 2011. She has reviewed and approved of this manuscript.

References Bloss, C. S., Schork, N. J., & Topol, E. J. (2011). Effect of direct-toconsumer genomewide profiling to assess disease risk. The New England Journal of Medicine, 364(6), 524–534. Kuehn, B. M. (2010). Inconsistent results, inaccurate claims plague direct-to-consumer gene tests. JAMA, 304(12), 1313– 1315. Kutz, G. D. (2010). Direct-to-consumer genetic tests: misleading test results are further complicated by deceptive marketing and other questionable practices. United States Government Accountability Office. http//www.gao.gov/new.items/d10847t.pdf. Accessed September 30, 2011. Palomaki, G. E., Melillo, S., Neveux, L., Douglas, M. P., Dotson, W. D., Janssens, A. C., et al. (2010). Use of genomic profiling to assess risk for cardiovascular disease and identify individualized prevention strategies–a targeted evidence-based review. Genetics in Medicine, 12(12), 772–784. Reis N.M. (2010). Analysis of privacy policies and practices of directto-consumer genetic testing companies: private sector databands and privacy protection norms. Representatives Office of Privacy Commisioner of Canada. http://www.law.ualberta.ca/centres/hli/ userfiles/file/Full%20Version%20OPCC%20Report%20March% 2028%202010.pdf. Accessed September 30, 2011. Salkovskis, P. M., & Rimes, K. A. (1997). Predictive genetic testing: psychological factors. Journal of Psychosomatic Research, 43(5), 477–487.