Direct-to-Consumer Genetic and Genomic Testing: Preparing Nurse Practitioners for Genomic Healthcare

Continuing Education

Direct-to-Consumer Genetic and Genomic Testing: Preparing Nurse Practitioners for Genomic Healthcare

Jennifer T. Loud ABSTRACT Rapidly emerging technologies make it possible for consumers to acquire information that is intended to explain their inherited susceptibility to disease and facilitate tailored healthcare services through directto-consumer (DTC) marketing of personal genetic (PG) and personal genomic (PGM) testing. However, the health benefits and risks associated with these technologies are largely unknown. Consumers will turn to their healthcare providers, including nurse practitioners, to interpret test results and seek guidance on how to use these test results for medical decision-making. Nurse practitioners will need to constantly update their practice skills in response to advances in genomic technology that create new expectations among patients and lead to substantial changes in healthcare delivery. Keywords: direct-to-consumer marketing, nurse practitioner, personal genetic testing, personal genomic testing © 2010 American College of Nurse Practitioners

Jennifer T. Loud, CRNP, DNP, is the assistant chief of the Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, of the National Cancer Institute in Rockville, MD. She can be reached at [email protected]. This continuing education activity is designed to augment the knowledge, skills, and attitudes of nurses and nurse practitioners regarding direct-to-consumer genetic testing and NP counseling opportunities. At the conclusion of this activity, the participant will be able to: a. Define DTC genetic/genomic testing and related key terms b. Analyze risks/benefits of genetic/genomic tests and ethical issues c. Explain why DTC genetic/genomic testing is an important health policy issue with application to essential genomic nursing competencies The author, reviewers, editors, nurse planners, and pilot testers all report no financial relationships that would pose a conflict of interest. The authors do not present any off-label or non-FDA approved recommendations for treatment. There is no implied endorsement by NPA or ANCC of any commercial products mentioned in the article.

Premier subscribers and ACNP members may receive the free 1.0 CE credit by reading the article and answering each question online at www.npjournal.org, or you may mail the test answers and evaluation, along with your processing fee check for $10 made out to Elsevier, to PO Box 540, Ellicott City, MD 21041-0540. Required minimum passing score is 70%.This educational activity is provided by Nurse Practitioner Alternatives.™ Nurse Practitioner Alternatives™ is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

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ecent discoveries in genetics (Figure 1) and genomics (Figure 2) have the potential to revolutionize the way healthcare is practiced. Advances in genomics and genetics have received a great deal of media attention, both positive and negative,1,2 which has led to a wide-ranging discussion within www.npjournal.org

healthcare professional organizations about whether any of these tests are ready to be integrated into primary care. Direct-to-consumer (DTC) marketing of personal genetic (PG) tests and personal genomic (PGM) tests has greatly increased the availability of these products to consumers, creating the opportunity for direct access to new The Journal for Nurse Practitioners - JNP

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Figure 2. Genome

Figure 1. Genetic

http://ghr.nlm.nih.gov/glossary=genome http://ghr.nlm.nih.gov/glossary=geneticcode

technologies without the involvement of healthcare providers, but to a large extent, the health benefits and risks associated with these technologies are unknown.3,4 One of the goals of the Human Genome Project was to enable people to explore their genome with information provided by new genetic and genomic technologies, while enhancing the value, options, and effectiveness of medical care. As our nation debates how to contain costs within our healthcare system, what are the current and emerging data regarding the usefulness of PG and PGM tests in healthcare?5 Traditionally, clinical genetic testing is considered after a detailed individual and family risk assessment has been performed by a healthcare provider (physician, advanced practice nurse, or genetic counselor) who uses hereditary single gene disorder “red flags” as testing indi-

cators (Table 1).6 This practice paradigm is based on our experience with classical Mendelian traits, which typically cluster in families and arise from rare mutations in highly penetrant mutations (i.e., confer very high risks of disease, such as lifetime risks of 30% to 100%, or relative risks that are 20- to 100-fold greater than normal).7 Healthcare providers are guided by professional practice guidelines on the use of genetic and genomic information in health-related decision-making.8 The consumer is provided with pre-test risk assessment, genetic education, and counseling before informed consent for genetic testing is obtained. Once informed consent is obtained, the appropriate genetic test is ordered by the healthcare provider, and an appointment is scheduled to disclose the results. At the disclosure appointment, classically face to face, the consumer receives an interpretation of the test result and a discussion about the current recommendations for risk management, including current methods in

Table 1. Red Flags that Should Prompt a Clinician to Consider a Genetic Cause or Contribution to a Patient’s Condition5 Family History

Multiple affected relatives in multiple generations on one side of the family

Group of congenital anomalies

Two or more anatomic anomalies in an individual

Extreme or exceptional presentation of a common condition

Early onset cardiovascular disease, cancer, or renal failure. Recurrent miscarriage. Bilateral primary cancers in paired organs (e.g., bilateral breast cancer), multiple primary cancers of different tissues in the same individual

Neurodevelopmental delay or degeneration

Developmental delay in a young child, developmental regression in children, or early onset dementia in adults

Extreme or exceptional pathology

Unusual tissue histology, such as pheochromocytoma, acoustic neuromas, medullary thyroid cancer, multiple colon polyps, plexiform neurofibromas, most pediatric malignancies

Surprising laboratory values

Transferrin saturation of 65%, potassium of 5.5 mmol/L, and sodium of 128 mmol/L in an infant; cholesterol of > 500 and unconjugated bilirubin of 2.2 mg/dL in a healthy 25-year-old

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Table 2. Examples of PG and PGM Tests9, 10 Test Name

Type of Test

How Test is Purchased

23andMe

Susceptibility testing for common diseases, traits, and ancestry testing

DTC via Internet

Consumer Genetics

Fetal gender; caffeine, alcohol and drug metabolism

DTC via Internet

DNADirect

-1 antitrypsin deficiency; Ashkenazi Jewish carrier screening; blood clotting disorders; breast and ovarian cancer; colon cancer screening; cystic fibrosis; diabetes risk; drug response panel; hemochromatosis; infertility; recurrent pregnancy loss

DTC via Internet; genetic counselors available by phone

Genetic Health (UK)

For males: genetic predisposition to prostate cancer, thrombosis, osteoporosis, metabolic imbalances of detoxification, and chronic inflammation

DTC via Internet; most services include a medical consultation

For females: genetic predisposition to breast cancer, bone metabolism (osteoporosis), thrombosis, cancer, and long-term exposure to estrogens Pharmacogenetic test for CYP450 genes, which influence how the liver metabolizes a large number of commonly prescribed drugs Health Tests Direct

More than 400 blood tests, including a few genetic tests (cystic fibrosis carrier screen, Factor V Leiden)

DTC via Internet

Holistic Health

Nutrigenomic test: comprehensive methylation panel with methylation pathway analysis Variety of nutritional supplements

Not described

Navigenics

Risk analysis for more than 20 common diseases, such as prostate cancer and diabetes

DTC via Internet

prevention or early detection of the particular disease being considered.9 In contrast, when vendors use DTC marketing of PG or PGM tests, the tests are advertised through print media, television media, or over the internet. A test kit may be purchased directly from the company, and consumers may receive test results by phone, mail, or email. A healthcare professional may or may not be involved in ordering and interpreting the test results (Table 2).9,10 Current PG and PGM tests include single gene (Figure 3) tests for Mendelian disorders and a broad array of newly developed molecular, cytogenetic, and biochemical methods of analyzing deoxyribonucleic acid (DNA), ribonucleic acid (RNA), protein products, gene polymorphisms (Figure 4), and chromosomes (Figure 3).11 More than 1,400 clinical PG tests are currently available, and most are ordered by a healthcare provider.12 www.npjournal.org

Many PG tests are developed and performed within a single laboratory that has clinical and research experience in the disorder of interest.11 Clinical PG testing is regulated by the Clinical Laboratory Improvement

Figure 3. Genes: Sequence of DNA that is a specific set of instructions for a particular protein or biological function

Photo from: http://ghr.nlm.nih.gov/handbook/basics/chromosome The Journal for Nurse Practitioners - JNP

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Table 3. Pharmacogenomic Test Examples13 Drug Response

Gene-SNP

Antidepressant Response

ABCB1/ rs2032583

Beta-Blocker Response

ADRB1/ rs1701253

Caffeine Metabolism

CYP1A2/ rs762551

Flourouracil Toxicity

DPYD mutations

Statin Response

COQ2/rs4693596

Warfarin Sensitivity

CYP2C9*2/rs1799853 and CYP2C9*3/ rs1057910

Amendments of 1988 (CLIA), which imposes quality control on the laboratory, personnel, documentation, and analytic validity of the genetic test. (Figure 5).11,12 PGM tests, in contrast to PG tests, are designed to provide either a comprehensive genetic risk profile for many diseases or a specific genetic risk profile.8 PGM tests may include diagnostic, predictive, pharmacogenomic (Table 3 ), and/or risk assessment testing, but many of tests being advertised and sold over the internet have not undergone clinical evaluation.2 Often the risks identified with these new tools are based on common alterations (mutations) in low-penetrance genes, which are often associated with relative risks of 1.2 to 2.0. While some tests offer genetic information that is more related to curiosity (e.g., the genetic variants related to earwax types),14,15 others claim that the tests may be used to permit early disease detection (i.e., screening) on the reasonable but often-unproved belief that “early detection” will improve long-term survival or to predict the future risks of developing specific diseases (e.g., Alzheimer disease or breast, colorectal, lung, ovarian, prostate, and gastric cancer, Table 2).10,16 However, the value of these tests in making decisions about healthcare interventions and the personal ramifications of testing (the risks and benefits) remain unclear or unexamined. METHODS TO EVALUATE PG AND PGM TESTS The Center for Disease Control’s Office of Public Health Genomics independent working group, Evaluation of Genomic Applications in Practice and Prevention (EGAPP), formalized the ACCE (Figure 5) framework to evaluate genetic and genomic tests8,17 This model can be used to evaluate PG and PGM tests as they are developed for implementation into healthcare services. By using this model, the analytic validity, clinical validity, clinical utility, 588

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Figure 4. Single Nucleotide Polymorphism (SNP): Single nucleotide poymorphisms are DNA sequence variations that occur when a single nucleotide (A,T,C, or G) in the genome sequence is altered.

http://www.ornl.gov/sci/techresources/Human_Genome/faq/ snps.shtml

and the ethical, legal, and social issues related to each type of PG or PGM test can be evaluated. When considering each PG or PGM test, ask: • Is the intended purpose of the test clearly stated? • Is there proof that the test result accurately identifies the genotype of interest and that the test result is reproducible? • Is there evidence that a PG or PGM test accurately and reproducibly identifies the risk of disease or the disease of interest? • Is there evidence that by identifying the risk of a disease, there are medical or lifestyle interventions that can lead to a reduction in the incidence, morbidity, or mortality related to the risk of disease or the disease of interest? These are some of the questions that need to be answered before PG and PGM can enter routine clinical practice. It is difficult to overcome the widely held view that no harm can come from attempting to learn more about a disease risk, but the costs and morbidity resulting from an ineffective test can be substantial, particularly at the cumulative societal rather than the individual level. Such adverse consequences may include: • Erroneous results, both false-negative (e.g., a breast cancer risk profile that falsely identifies a women as low risk when, by family history alone, she is at high risk) and false-positive (a heart disease profile that identifies an individual at high risk for cardiovascular disease in an individual who has no familial or clinical indications of cardiovascular disease) Volume 6, Issue 8, September 2010

Figure 5. CDC’s Evaluation of Genomic Appilcations in

Figure 6. Personal Utility8

Practice and Prevention (EGAPP)

Public Health Genomics, 2009

• Potentially enormous increases in healthcare costs related to the evaluation of abnormal findings that result from a test, most of which turn out to be false-positives • Risk of increasingly invasive diagnostic procedures, sometimes culminating in unnecessary surgery, in an effort to define the basis for the test abnormality A recent National Institutes of Health-CDC Multidisciplinary Workshop8 developed recommendations to strengthen the scientific foundation of PG and PGM tests, including recommendations to: • Develop and implement scientific standards for personal genomics • Develop and implement a multidisciplinary research agenda • Enhance credible knowledge synthesis and dissemination of information to providers and consumers • Link scientific research on validity and utility to evidence-based recommendations for the use of personal genomic tests • Consider the value of personal utility (Figure 6) As the number PG and PGM testing services that offer comprehensive or targeted genetic risk profiles related to disease risk increases, consumers of these services will look to nurse practitioners (NPs) for accurate information and interpretation of the genetic and genomic content. POTENTIAL BENEFITS OF DTC MARKETING While there is widespread concern about the scientific underpinnings of PG and PGM testing, it is also possible that DTC marketing of these tests may encourage consumers and healthcare providers to become more proactive in health promotion, documentation of individual and family health history, and early detection of disease and disease management.17 Ideally, PG and PGM tests www.npjournal.org

will provide information that can be used for risk assessment along a continuum of disease natural history, from primary to quaternary prevention.8 In an ideal setting, the information gained from testing may inform healthcare decision-making related to: • Primary prevention: leading to a reduction of disease incidence (e.g., susceptibility testing for cancer, type 2 diabetes, coronary heart disease with primary disease prevention through chemoprevention, cholesterol reduction, weight loss) • Secondary prevention: identifying persons at significantly increased disease risk (e.g., susceptibility testing for prostate cancer and colorectal cancer), followed by early targeted screening (assuming the existence of a proven screening modality) with potential for detecting disease at an earlier, more readily treatable stage in its natural history • Tertiary prevention: leading to personalized treatments (e.g., testing for genetic variants in drugmetabolizing genes that make it more or less likely that an individual will benefit from or be harmed by exposure to a particular medication). Theoretically, identifying such genetic variants could result in reducing drug dose to avoid a predictable toxicity or deciding not to use a medication in someone unlikely to benefit from its administration (e.g., personalized prescriptions for warfarin or chemotherapy). • Quaternary prevention: leading to improved quality of life, improved psychosocial outcomes or palliative care (e.g., susceptibility testing to diseases with no available interventions, such as Huntington’s chorea. Some adults who are at high genetic risk of this condition choose to test and are found not to carry the mutation that leads to it. Knowledge of their mutation status may lead to improved quality of life by removing the fear of developing Huntington’s disease as they age). The Journal for Nurse Practitioners - JNP

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Despite the lack of evidence to support integrating testing be offered only if there are interventions that will most PG and PGM tests into routine clinical practice today, lead to reduced risk of disease or improved morbidity or DTC marketing may provide an impetus for all healthcare mortality related to the disease.18 Protecting children from providers, and NPs in particular, to regularly review an unnecessary PG and PGM testing has not been clearly individual’s family history and to support consumers’ efforts addressed by the many companies that sell the tests.19,20 In to achieve a healthy lifestyle. addition, there is limited regulaHowever, further research is tory oversight of PG and PGM needed to determine the specific test services, and many of the The value of these tests in effects of PG and PGM testing tests being marketed DTC are making decisions about 8 on health outcomes. not performed under the healthcare interventions Centers for Medicare & and the personal POTENTIAL RISKS OF DTC Medicaid Services (CMS) CLIA MARKETING standards. As the human conseramifications of testing (the There is an urgent need for all quences of DTC marketing of risks and benefits) remain healthcare providers to become PG and PGM come into focus, unclear or unexamined. familiar with PG and PGM testnew regulatory options may ing and to develop sufficient skills need to be considered. Indeed, in interpreting results and comthe US Food and Drug municating genetic and genomic risk to understand what to Administration (FDA) recently notified six companies that do next. In particular, primary care providers need to market PG and PGM tests directly to consumers that their develop these skills as genetic and genomic technologies products are considered medical devices, which must be enter the public domain and clients bring test results to clifederally approved as safe and effective.21 The FDA asked nicians for interpretation. In a recent internet-based interthese six companies to submit their products for review. view of individuals who considered using DTC-marketed PG and PGM testing, researchers found that the individuals PG AND PGM TESTS AND PROFESSIONAL would seek help in interpreting the test results from their ORGANIZATIONS personal physician.1 The concern, of course, is that the pubSeveral nursing professional organizations (Oncology lic may begin to use PG and PGM tests before the analytic Nursing Society, International Society of Nurses in validity, clinical validity, or clinical utility are known and Genetics, American Nurses Association22-24) have develincrease pressure on an already overstretched healthcare sysoped position statements and credentialing programs for tem. In view of the well-documented shortages of fully nurses seeking to practice in genetic healthcare. The positrained genetics professionals, there are career opportunities tion statements reflect the need for nurses at all levels to for the NPs who wish to acquire special expertise in genetic contribute to the following: risk assessment and management (see below). • Education of patients, families, and the public DTC marketing of PG and PGM tests could lead to regarding genetic risk25 unnecessary diagnostic, pharmacologic, and surgical inter• Integration of genetic information into nursing prac1 ventions. Will DTC of PG and PGM tests lead to tice as new genetic information becomes available requests for services that are not indicated, as was the case • Development of continuing education programs in with DTC of whole body scans? Concern has also been genetics and genomics for practicing nurses raised that PG and PGM testing could lead to consumer • Collaboration with other genetic healthcare profespreference for pharmaceuticals and services of questionsionals and organizations to provide comprehensive able benefit or create a false sense of reassurance, leading care to individuals at high genetic risk of disease to reduced compliance with standard recommendations Advanced practice nurses with specialty training in for healthy lifestyles and screening for the common genetics may also provide comprehensive genetic risk 3 adult-onset diseases. assessment services for the following: The current guidelines for predisposition genetic testing • Risk assessment of children younger than 18 recommend that predisposition • Pre- and post-test counseling and follow-up 590

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• Provision of personally tailored risk management options and recommendations • Psychosocial counseling and support services The International Society of Nurses in Genetics developed two credentialing programs for nurses who wish to document their expertise in genetic healthcare: • Nurses with a master’s degree in nursing may qualify for the Advanced Practice Nurse in Genetics (APNG) credential. • Nurses with a baccalaureate degree in nursing may qualify for the Genetics Clinical Nurse (GCN) credential. Both credentials document a nurse’s ability to obtain a pedigree, evaluate the presence or absence of hereditary risk, assess the likelihood of a hereditary syndrome, provide genetic information and psychosocial support to individuals and families, and provide nursing care to individuals and families affected by genetic diseases. An APNG also provides genetic counseling services (including pre- and post-test counseling), facilitates genetic testing, and interprets genetic test results. A number of professional healthcare organizations have voiced concern about the clinical validity and the clinical utility of PG and PGM testing12,26,27 and have developed position statements on DTC marketing that address the performance characteristics of the tests and the ethical, legal, and social implications (ELSI) of these technologies. Overall, there is broad agreement among the organizations that companies offering DTC PG and PGM testing should comply with existing practice and ethical standards of genetic testing. All agree that basic elements of informed consent for predisposition testing should include: • Information on the specific PG or PGM test being performed • Implications of a positive and negative test result • Possibility that the test will not be informative • Options for risk estimation without PG or PGM testing • Risk of passing a mutation, or risk, to children • Technical accuracy of the test • Fees involved in testing and counseling • Psychological implications of the test result • Risks of insurance or employer discrimination • Confidentiality issues • Options and limitations of risk management and strategies for prevention following testing www.npjournal.org

• Importance of sharing genetic test results with at-risk relatives so that they may benefit from this information in making their own healthcare decisions FUTURE APPLICATIONS OF PERSONAL GENETICS AND GENOMICS Breast Cancer Risk Assessment The National Cancer Institute’s Breast Cancer Risk Assessment Tool (BCRAT, previously known as the Gail Model) is the most frequently used model for estimating breast cancer risk in clinical practice (available at www.cancer.gov/bcrisktool). It is based on a casecontrol analysis of data from the Breast Cancer Detection Demonstration Project, which was a joint American Cancer Society (ACS) and National Cancer Institute (NCI) breast cancer screening study that involved 280,000 women between the ages of 35 and 74.28 The BCRAT model incorporates variables that have been associated with an increased a risk of developing female breast cancer, including a woman’s personal history of prior breast biopsies and whether atypical hyperplasia was detected, her reproductive history (age at menarche and age at the first live birth), and the history of breast cancer among her first-degree relatives (mother, sisters, and daughters) in order to estimate the 5-year and lifetime risk of breast cancer. The BCRAT is advantageous in that it permits estimating the combined effect of multiple major breast cancer risk factors and can compare an individual woman’s breast cancer risk versus women in the same age group from the general population. The model has been shown to be well validated and calibrated in women from the general population.28 However, it does not account for paternal family history, second-degree relatives, age-at-onset of cancer in relatives, bilateral cancers, multiple primaries, or other cancers, and it does not account for the presence of inherited genetic predisposition. The model is most applicable to women from the general population who present for routine breast cancer screening and not appropriate where genetic predisposition is suspected (e.g., germline BRCA1 or BRCA/2 mutation). Women over 35 with a BCRAT score ⱖ 1.67 have a 5-year risk of developing breast cancer that is similar to a 60-year-old woman and are considered to be at moderately elevated risk of breast cancer. In women with this level of risk, it is reasonThe Journal for Nurse Practitioners - JNP

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Table 4. Seven SNP Genotypes Associated with Breast Cancer31-33 Location Gene Chromosome SNP

Disease Odds Ratio Allele Frequency per Allele

FGFR2 10q25.3-26 rs2981582

0.38

1.26

TNRC9 (or TOX3) 16q12.1 rs3803662

0.25

1.20

MAP3K1 5q11 rs889312

0.28

1.13

LSP1 11p rs3817198

0.30

1.07

CASP8 2q rs1045485

0.87

1.14

8q rs13281615

0.40

1.08

2q35 rs13387042

0.497

1.20 Geometric mean 1.15

able to consider screening before the age of 40, and it may be reasonable to consider chemoprevention of breast cancer with tamoxifen.28 In a recent report, Dr. Gail explored the impact of adding single-nucleotide polymorphism (SNP) genotypes (Table 4) to the BCRAT in an effort to improve the discriminatory accuracy (e.g., the area under the curve or AUC) of breast cancer risk prediction.30 The investigator compared breast cancer risk classification using the BCRAT with g the BCRAT plus two different panels of SNP genotypes (BCRATplus7 and BCRATplus11). These genetic variants have been confirmed in multiple large studies to each confer a small (e.g., relative risk ⫽ 1.2) risk of breast cancer in both sporadic and hereditary breast cancer.31-33 Risks of this magnitude cannot be practically leveraged for clinical decision-making, but the hope has been that combining panels of SNPs might be a more effective strategy. Findings from the analysis by Gail demonstrated that the addition of the polymorphism genotypes improved the discriminatory accuracy of breast cancer risk classification by a small amount (AUC of BCRAT vs BCRATplus7 ⫽ 0.607 vs. 0.632; AUC of BCRAT 592

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vs. BCRATplus11 ⫽ 0.607 vs 0.585; AUC of BCRATplus7 vs BCRATplus11 ⫽ 0.632 vs 0.637). While this analysis demonstrated an improvement in breast cancer risk classification using BCRAT with the SNP genotypes, the improvement was so small that the author concluded the difference was not clinically meaningful. Further studies are needed to validate breast cancer risk prediction models that incorporate SNP genotypes to more accurately assess if and by how much they improve risk classification over the BCRAT alone. Individual Whole-Genome Sequencing Recent advances in high-throughput DNA sequencing technologies have led to immense improvements in the cost and speed of individual whole-genome sequencing.34 A number of groups35-38 have reported their methods of individual whole-genome sequencing and demonstrated the speed with which innovation occurs and drives down the cost of sequencing. The 1000 Genomes Project, a collaboration between researchers in the United States, United Kingdom, Germany, and China,39 aims to sequence the genomes of a large number of people to provide a comprehensive resource on human genetic variation. The primary goal is to find genetic variants that have frequencies of at least 1% in the populations studied (currently, European, East Asian, West African, Americas, and South Asian), with the limitation that the project lacks phenotypic information on the individuals who contributed DNA for the project. To overcome the lack of phenotypic information in the 1000 Genomes Project, The ClinSeq Project was developed to pilot large-scale genome sequencing for research in genomic medicine at the National Institutes of Health Clinical Research Center in Bethesda, MD.40 The study seeks to enroll 1000 individuals who will be evaluated for personal health status and family history. The project aims to: • Develop the infrastructure to acquire and analyze genome sequence from individual research participants • Pilot the use of large-scale genome sequencing to understand the genetic architecture underlying human traits • Build an open, shared resource for basic and clinical research in genomic medicine • Establish an approach for informed consent and the disclosure of genetic information to research subjects in large-scale medical sequencing studies Volume 6, Issue 8, September 2010

Atherosclerotic heart disease (AHD) is the prototype disease being evaluated because of its frequency, recognizable subphenotypes (e.g., hypercholesterolemia, hypertension, angina, myocardial infarction), complex genetic architecture, association with a set of genes that can be sequenced using conventional technology, and variety of treatment options to decrease the risk among high-risk individuals Overall, the ClinSeq project aims to extend the clinical practice of medical genetics from dealing with rare, highly penetrant diseases into more common, lower-penetrant diseases, particularly those diseases where early identification may lead to interventions to lower the risk of developing the disease. CONCLUSION Integrating rapidly emerging genetic and genomic findings into evidence-based healthcare recommendations is a challenge for all healthcare providers. NPs’ patients depend on their advice and experience to inform healthcare and health management decisions. Integrating new ways to improve risk prediction, disease prevention, and early detection is an essential function of all primary care providers, but evaluating the evidence for practice and determining whether the evidence is sufficient for a test to be integrated into primary care is a challenge for all. As the evidence for practice is established with new genetics and genomic technologies, NPs will strive to integrate these technologies into practice. By understanding the benefits, risks, and limitations of genetic and genomic technologies, NPs strive to enhance their patients’ understanding, decision-making, and health outcomes. On the near horizon, NPs must expand their understanding of genome-wide association studies, candidate gene association studies, and large-scale medical sequencing to knowledgeably participate in the broad healthcare discussion regarding: • Whether specific genetic polymorphisms are meaningfully associated with disease risks • Why personal genome scans may or may not be ready for integration into healthcare decision-making • Why there may be emotional or psychological risk associated with particular findings of genetic association studies and disease prediction • How to protect individual rights while maximizing scientific discovery www.npjournal.org

• How new genetic and genomic information affects the ethics of health care, particularly related to privacy and confidentiality • How to weigh or balance the risks and benefits associated with these new technologies Advances in genetic and genomic information will increasingly influence healthcare decisions and influence how nursing practice changes over time. In response to ever-changing healthcare needs, several professional nursing organizations (ONS and ISONG), have developed position statements related to the use of genetic information and nursing practice for nurse generalists, advanced practice nurses, and those with specialty training in genetics. The advent of the professional credentialing process in genetics through ISONG for the generalist nurse and the advanced practice nurse (APNG) adds a new level of recognition to the subspecialty of genetic nursing. NPs may want to consider seeking further educational opportunities to support their understanding of genetics and genomics or to consider seeking advanced credentialing in genetics. NPs, in all areas of practice, deliver healthcare to improve patient outcomes through evidence-based interventions and research to define best practices. NPs will continue to contribute to the understanding of nursingsensitive, patient-specific genetic outcomes within primary and subspecialty practices, including the following: • Patient outcomes after interventions that provide new genetic services • How healthcare systems deliver, or use, new genetic and genomic services • The desirability and consequences of implementing genetic screening to identify those in need of genetic or genomic services at the population level • How genetic and genomic information affects individuals and families • How genetic and genomic policy affects access to healthcare and the use of genetic and genomic services • Whether there are barriers to or facilitators of patient access to genetic and genomic services • The potential risks and benefits of pharmacogenetics and pharmacogenomics in healthcare NPs will continue to advocate for high-quality patient care during the transition from pregenomic healthcare to postgenomic healthcare. As electronic medical records improve the safety and efficiency of healthcare, NPs will safeguard patient privacy rights and The Journal for Nurse Practitioners - JNP

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protect against discrimination. Healthcare delivery systems will continue to change as evidence for practice is established and implemented. NPs will continue to evolve their practice in response to the needs of society and rapid changes in healthcare, as all nursing practice has done since the beginning of the profession. References 1. McGuire AL, Burke W. An unwelcome side effect of direct-to-consumer personal genome testing: raiding the medical commons. JAMA. 2008;300:2669-2671. 2. Caulfield T, Ries NM, Ray PN, Shuman C, Wilson B. Direct-to-consumer genetic testing: good, bad or benign? Clin Genet. 2009;77:101-105. 3. Manolio TA, Brooks LD, Collins FS. A hapmap harvest of insights into the genetics of common diseases. J Clin Invest. 2008;18:1590-1605. 4. Feero WG, Guttmacher AE, Collins FS. The genome gets personal, almost. JAMA. 2008;299:1351-1352. 5. Feero WG, Guttmacher AE, Collins FS. Genomic Medicine – An updated primer. N Engl J Med. 2010;362:2001-2011. 6. Genetics Through a Primary Care Lens: A Web-Based Resource for Faculty Development. Available at: http://staff.washington.edu/sbtrini/index.shtml. Accessed December 30, 2009. 7. Jorde LG, Carey JC, Bamshad MJ. Medical Genetics. 4th ed. Philadelphia: Mosby/Elsevier; 2010. 8. Khoury MJ, McBride C, Schully SD, Ioannidis JPA, Feero WG, Janssens ACJW, Gwinn M, et al. The scientific foundation for personal genomics: recommendations from a National Institutes of Health/Centers For Disease Control and Prevention multidisciplinary workshop. Genet Med. 2009;11:1-9. 9. Genetic Home Reference. What is direct-to-consumer genetic testing? Available at http://ghr.nlm.nih.gov/handbook/testing/directtoconsumer. Accessed September 25, 2009. 10. Hogarth S, Javit G, Melzer D. The current landscape for direct-to-consumer genetic testing: legal, ethical, and policy issues. Annu Rev Genomics Hum Genet.2008;9:161-82. 11. Secretary’s Advisory Committee on Genetics, Health & Society. U.S. System of oversight of genetic testing: A response to the charge of the Health & Human Services. 2008 April. Available at: http://www4.od.nih.gov/oba/ SACGHS/reports/SACGHS_oversight_report.pdf. Accessed September 25, 2009. 12. Hudson K, Javitt G, Burke W, Byers P. ASHG statement on direct-toconsumer genetic testing in the United States. Ob Gynec. 2007;110:1392-1395. 13. Zhou SF, Di YM, Chan E, Du YM, Chow VDW, Xue CC, et al. Clinical pharmocogenetics and potential application in personalized medicine. Cur Drug Metab. 2008;9:738-784. 14. Bowen DJ, Harris J, Jorgensen CM, Myers MF, Kuniyuka A. Socioeconomic influences on the effects of a genetic testing direct-to-consumer marketing campaign. Public Health Genomics. 2010;13(3):131-142. 15. Goddard KA, Duquette D, Zlot A, et al. Public awareness and use of directto-consumer genetics tests: results from 3 state population-based survey, 2006. Am J Public Health. 2009;99(3):442-5. 16. Berg C, Fryer-Edward K. The ethical challenges of direct-to-consumer genetic testing. J Bus Ethics. 2008:77:17-31 17. Public Health Genomics. Genomic translation: ACCE Process model for evaluating genetic test. Available at: http://www.cdc.gov/genomics/ gtesting/ACCE/index.htm. Accessed September 25, 2009. 18. Hunter DJ, Khoury MJ, Drazen JM. Letting the genome out of the bottle: will we get our wish? N Engl J Med. 2008;358:105-107. 19. National Cancer Institute. Genetics Overview (PDQ) 2008. Available at: http://www.cancer.gov/cancertopics/pdq/genetics/overview/HealthProfession al/page5 and http://www.cancer.gov/cancertopics/pdq/genetics/riskassessment-and-counseling/HealthProfessional/page4#Section_188. Accessed November 23, 2009. 20. Genetics & Public Policy Center. Direct-to-Consumer genetic testing: Empowering or endangering the public? 2008b, May 30. Available at: http://www.dnapolicy.org/policy.issue.php?action⫽detail&issuebrief_id⫽32. Accessed September 25, 2009. 21. US Food and Drug Administration. In Vitro Diagnostics. Available at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDi agnostics/default.htm. Accessed June 15, 2010. 22. Oncology Nursing Society. The role of the oncology nurse in cancer genetic counseling. Available at: http://www.ons.org/publications/positions/ documents/pdfs/CancerGenetic.pdf Accessed November 23, 2009.

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Volume 6, Issue 8, September 2010