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It has been more than 10 years since the Human Genome Project first sequenced and analyzed our DNA. Now a growing number of companies are offering personal genome-testing kits directly to consumers. These tests provide information about susceptibility to disease, inherited traits, and individual pharmacologic responses.
Primary-care providers (PCPs) are increasingly expected to interpret the results from these genetic-test kits for patients, who often have questions about the validity and predictive ability of such products. Patients are also seeking advice on preventive screening and treatments regarding their genetic susceptibilities. Consequently, PCPs are being called upon to provide education, counseling, and psychosocial support for patients who perform home genetic tests.
What are DTC genetic-test kits?
Direct-to-consumer (DTC) home genetic-test kits claim to be able to detect traits and risk of disease, predict responses to drug treatment, and determine ancestry.1 Companies such as 23andMe, Navigenics, deCODE, and Pathway Genomics all offer DTC genetic test kits online for approximately $99.00 and assure confidentiality of results.
Websites such as 23andMe.com ask consumers to create an account and order the DNA kit from the site’s online store. The kit is shipped directly to the consumer, who then follows the instructions for DNA harvesting by means of buccal swab or saliva sample, and sends the kit back to the company to await results. Once the tests are completed, the consumer is notified and given “personalized” recommendations based on the genetic findings.3
On November 22, 2013, the U.S. Food and Drug Administration (FDA) ordered the 23andMe genomics company to cease marketing its Saliva Collection Kit and Personal Genome Service (PGS). The FDA asserted that the product is an unapproved and uncleared diagnostic device with questionable validity. Navigenics and deCode have also withdrawn genetic test kits from the market. It remains to be seen if these companies will reintroduce their products.
How DTC genetic-test kits work
DTC genetic tests are based on genome-wide association studies (GWAS). A GWA study scans complete sets of DNA of a population to find genetic variations associated with specific diseases. GWAS focus on markers of genetic variation, single-nucleotide polymorphisms (SNPs) —differences in the amino acids that make up DNA. If one type of SNP is seen more frequently in people with a disease, the SNP is said to be “associated” with the disease.5,6
It is important to understand that SNPs do not directly cause disease; they are commonly found in persons with the given disease. SNPs cannot be solely relied upon for prediction of disease because it is combinations of gene mutations and environmental factors that most often cause disease, rather than an SNP.
Four types of tests in a kit
Four different types of tests are included in a DTC genetic-test kit. One test shows single gene mutations that have strong genotype-phenotype correlations. These include common Mendelian disorders such as cystic fibrosis, Huntington disease, and beta thalassemia
Another test can identify particular genetic variants that affect metabolism of certain drugs. An additional test indicates the consumer’s risk for polygenic complex diseases such as cardiovascular disorders, diabetes, cancers, and osteoporosis. Finally, there are genetic tests that can confirm or deny paternity based on DNA test results.1
As our knowledge of the human genome expands, more diseases, conditions, and drug responses are being added to the list of what can be detected through DTC genetic-test kits.
Benefits and drawbacks of DTC genetic-test kits
Proponents of genetic-test kits contend that providing this information directly to consumers could result in improved patient compliance with health screening and preventive health-care practices. Consumers may become more conscientious about lifestyle changes that reduce their risk of disease development.
The tests could also motivate consumers to make proactive decisions regarding preventive treatments.For example, BRCA1/BRCA2 gene mutations are a common topic of discussion among patients and primary-care providers. Studies show that providing information regarding inheritance of and mutations increases awareness of ovarian cancer and of breast cancer screening and prevention among patients and their families.
Once they learn that they carry these mutations, women often choose to undergo risk-reducing procedures such as bilateral mastectomies and oophorectomies.
Skeptics of DTC test kits, however, are concerned that a false prediction of increased risk of disease and confusing results can cause anxiety for patients and lead to unnecessary tests, procedures, and costs without proper guidance from health-care professionals. Conversely, consumers who receive falsely reassuring results could neglect to obtain needed screening tests or to follow necessary preventive measures.
According to research, the DTC genetic-test kits are proficient in predicting the risk of some highly inheritable monogenic diseases.However, when it comes to such complex diseases as cancer and diabetes, many factors play a role in a person’s risk.
A complex disease usually develops based on the interplay between more than one genetic mutation and nongenetic factors such as diet, exercise, smoking status, and alcohol use.Because of these variables, experts say that complex diseases cannot be predicted using DTC genetic-test kits. In addition, studies are starting to show that home genetic-test kit results often vary among test-kit manufacturers.
This raises questions about the reliability of findings.Finally, genetic-test-kit results are based on a Caucasian reference population. When calculating risks, these products do not account for ancestry of consumers who are non-Caucasian.
PCPs and genetic testing
PCPs have expressed both positive and negative reactions to DTC test kits. In one Web-based study, approximately 40% of PCPs reported that they would tailor the health-care management of a patient to the results of genetic-test kits.10
For patients showing an increased risk for Alzheimer disease, they would suggest more frequent early screening for dementia; order more computed tomography, magnetic resonance imaging, and positron emission tomography scans; and educate these patients regarding disease prevention.
For persons whose results showed an increased risk of glaucoma, PCPs said they would recommend eye exams more often. PCPs made similar statements regarding patients whose tests revealed an increased risk of cardiovascular disease and type 2 diabetes, saying they would place more emphasis on pertinent lifestyle changes for these individuals and perform more frequent screening and laboratory tests.
Although manufacturers of the DTC genetic-test kits do refer consumers to a genetics counselor specified on the label, studies show that less than 10% of customers utilize the kit’s recommended counselor. Instead, pharmacists and PCPs are being consulted most often regarding the results yielded by these products.1
The majority of member-physicians of the American Medical Association do not feel prepared to implement FDA-approved genetic-testing recommendations in their practice: A study of family-practice physicians indicated that more than 75% feel they need more education regarding genetic aspects of patient care.12
Many PCPs underwent their education and training prior to the current upsurge in information regarding genomics, and studies show patients sense that PCPs are unprepared in the area of genetics. A 2011 national survey revealed that only 17% of Americans believed their provider to be up-to-date and knowledgeable about genomics-based medicine.10,13-17
Necessary proficiency of the PCP
The PCP is in an ideal position to evaluate and treat patients for genetic disease because primary care combines treatment of acute illness with disease prevention and anticipatory guidance. Experts contend that PCPs need to incorporate basic genomic competencies into their daily practice, including the following:
Identify individuals who have increased genetic risks.PCPs need to recognize key information in the patient history that indicates risk of a genetic disorder. Every patient warrants a comprehensive family history, and charting a three-generation pedigree on the patient is ideal.
A pedigree can identify other at-risk family members who might benefit from genetics counseling or testing. Patients can chart their own family pedigree using a tool from the U.S. Surgeon General, available at My Family Health Portrait.
Distinguish physical features of common genetic conditions.The PCP should have knowledge of specific dysmorphic characteristics that raise suspicion of genetic disorders.
Refer patients with genetic susceptibilities for appropriate screening and diagnostic tests.The identification of certain genetic susceptibilities in a given patient should be followed by appropriate referrals for screening and diagnostic tests.
Monitor the health of individuals with a genetic disorder.PCPs in collaboration with appropriate subspecialists should work to monitor the health of patients with a genetic disorder or those at increased risk of harboring a genetic disorder.
Provide basic genetic information to patients and families.By providing information regarding genetics to patients and families, PCPs are able to help patients make informed decisions.
Tailor patient treatment and management to genetic information.Some patients who receive genetic susceptibility information will opt to obtain preventive treatment. PCPs need to be well-informed about prophylactic treatments and procedures related to genetic susceptibility and be up-to-date in pharmacogenomics—the influence of genetics on medication metabolism and response.
Identifying individual gene differences can help customize medication choice and dosing regimen for the best patient response.
Provide collaborative health care.Individuals with complex genetic disorders or susceptibilities need a health-care team that works together to meet the patient’s needs. PCPs will have to incorporate the recommendations of other health-care providers into the patient’s plan of care.
Recognize psychosocial aspects of genetic testing and diagnosis.Genetic information can influence the emotional, psychological, and social health of patients. For example, such knowledge can provoke anxiety in some individuals. Genetic information of the patient may also be applicable to family members, making family genetics counseling necessary.
Appropriately refer patients to genetics counselors.PCPs are in the position to know which patients with genetic health-care needs require referral. Patients with a significant family history of genetic disorders should be referred to genetics counselors and medical specialists.
Genetics counselors can discuss the implications of highly penetrant gene mutations. These specialists are also more informed about the limitations of genetic testing, the potential repercussions for other family members, and other implications such as the effect on health-care costs.
Safeguard patient genetic information.The Genetic Information Nondiscrimination Act of 2008 (GINA) underscores the importance of confidentiality of genetic information and that the PCP should not provide patient genomic information to third parties without authorized patient permission.
Broaden knowledge base with continuing education in genomics.Research regarding genetics and genomics is emerging rapidly and patients are becoming increasingly cognizant of how genetics influences their health. PCPs will need to keep pace with this burgeoning field of knowledge.
The future of genomics in primary care
Patients are actively seeking knowledge about their unique susceptibilities and will soon be able to incorporate this information into their personal health-care management.6Although DTC genetic-test kits are being pulled from the market, more reliable versions will soon be available.
More accurate methods of genome analysis—whole genome sequencing (WGS) and whole exome sequencing (WES)—are currently used in specialized clinical settings,22and will become available for wider use.
WGS determines the complete DNA sequence of an organism’s genome at a single time. This entails sequencing all of the organism’s chromosomal DNA as well as DNA contained in the mitochondria. WES selectively deciphers the coding regions of the genome that are translated into proteins.
Currently, WGS and WES are used to identify specific gene changes in cancer cells to guide patient therapy, to identify a person’s inherited cancer risk, and to estimate prognosis. These methods of genome testing are unavailable for DTC use due to prohibitive costs, but are predicted to be more affordable and widely available in the near future for more extensive use.23
PCPs are increasingly being called upon to provide genetic information to patients and their families. PCPs need to interpret genetic-test results, assess genetic risk, order preventive screening tests and diagnostic tests, educate patients and their families, and advise patients about preventive treatments and follow-up. It is clear that PCPs need proficiency in genomics for daily practice.
For more information on integrating genomics into primary-care practice, refer to the Genetics in Primary Care Institute.20
Theresa Capriotti, DO, MSN, CRNP is a clinical associate professor at the Villanova University College of Nursing in Villanova, Pa.
Mary Kline is a BSN honors student at the Villanova University College of Nursing in Villanova, Pa.
- Patrinos GP, Baker DJ, Al-Mulla F, et al. Genetic tests obtainable through pharmacies: the good, the bad, and the ugly. Hum Genomics. 2013;7(1):17. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC3711749/.
- Bloss CS, Darst BF, Topol EJ, Schork NJ. Direct-to-consumer personalized genomic testing. Hum Mol Genet. 2011;20(R2):R132–141. Available at hmg.oxfordjournals.org/content/early/2011/08/24/hmg.ddr349.full.
- 23andMe, Inc. Information retrieved September 29, 2013, from www.23andMe.com.
- U.S. Food and Drug Administration. Inspections, Compliance, Enforcement, and Criminal Investigations Warning Letter: 23andMe, Inc. 11/22/13. Available at www.fda.gov/iceci/enforcementactions/warningletters/2013/ucm376296.htm
- Bloss CS, Schork NJ, Topol EJ. Effect of direct-to-consumer genomewide profiling to assess disease risk. N Engl J Med. 2011;364(6):524-534. Available at www.nejm.org/doi/full/10.1056/NEJMoa1011893#t=articleTop.
- Janssens ACJW, van Duijn CM. An epidemiological perspective on the future of direct-to-consumer personal genome testing. Investig Genet. 2010;1(1):10. Available at www.investigativegenetics.com/content/1/1/10.
- Schwartz MD, Isaacs C, Graves KD, et al. Long-term outcomes of BRCA1/BRCA2 testing: risk reduction and surveillance. Cancer . 2012;118(2):510-517. Available at onlinelibrary.wiley.com/doi/10.1002/cncr.26294/pdf.
- Dohany L, Gustafson S, Ducaine W, Zakalik D. Psychological distress with direct-to-consumer genetic testing: a case report of an unexpected BRCA positive test result. J Genet Couns. 2012;21(3):399-401.
- Skytte AB, Crüger D, Gerster M, et al. Breast cancer after bilateral risk-reducing mastectomy. Clin Genet. 2011;79(5):431-437.
- Bernhardt, BA, Zayac C, Gordon, ES, et al. Incorporating direct-to-consumer genomic information into patient care: Attitudes and experiences of primary care physicians. Per Med. 2012;9(7):683-692. Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684987/.
- Bloss CS, Topol EJ, Schork NJ. Association of direct-to-consumer genome-wide disease risk estimates and self-reported disease. Genet Epidemiol. 2012;36(1):66-70.
- Powell KP, Christianson CA, Cogswell WA, et al. Educational needs of primary care physicians regarding direct-to-consumer genetic testing. J Genet Couns. 2012;21(3):469-478.
- Cogent Research. Company press release via Business Wire: Americans skeptical of physicians’ knowledge of genomics. January 25, 2011. Available at www.businesswire.com/news/home/20110125006349/en.
- Pandey A. A piece of my mind. Preparing for the 21st-century patient. JAMA . 2013;309(14):1471-1472.
- Mainous AG 3rd, Johnson SP, Chirina S, Baker R. Academic family physicians’ perception of genetic testing and integration into practice: a CERA study. Fam Med. 2013;45(4):257-262.
- Goldsmith L, Jackson L, O’Connor A, Skirton H. Direct-to-consumer genomic testing from the perspective of the health professional: a systematic review of the literature. J Community Genet. 2013;4(2):169-180.
- Marshall E. Human genome 10th anniversary: waiting for the revolution. Science . 2011;331(6017):526-529.
- Loud JT. Direct-to-consumer genetic and genomic testing: preparing nurse practitioners for genomic healthcare. J Nurse Pract. 2010;6(8):585-594.
- Scott J, Trotter T. Primary care and genetics and genomics. Pediatrics . 2013;132(Suppl 3):S231-237. Available at pediatrics.aappublications.org/content/132/Supplement_3/S231.full.pdf+html.
- Genetics in Primary Care Institute (GPCI). Available at GeneticsInPrimaryCare.org.
- Feero WG, Guttmacher AE, Collins FS. Genomic medicine—an updated primer. N Engl J Med. 2010;362(21):2001-2011. Available at www.nejm.org/doi/full/10.1056/NEJMra0907175.
- Johansen Taber KA, Dickinson BD, Wilson M. The promise and challenges of next-generation genome sequencing for clinical care. JAMA Intern Med. 2014;174(2):275-280.
- Korf BR, Rehm HL. New approaches to molecular diagnosis. JAMA . 2013;309(14):1511-1521.
All electronic documents accessed May 15, 2014.