Clinical Aspects of Genomics: An Update

  • Cynthia A. Prows, MSN, CNS, FAAN 
    Cynthia A. Prows, MSN, CNS, FAAN 

    Ms. Prows received her BSN and MSN from the University of Cincinnati College of Nursing. In 1990 she became a clinical nurse specialist in genetics; since that time she has published over 20 articles about genetics in peer reviewed nursing and medical journals. She directs the Genetics Education Program for Nurses which provides web-based genetics continuing education opportunities for nurses as well as web-based instructional resources for nursing faculty. Ms. Prows recently completed a four year appointment with the Health Resources and Services Administration’s National Advisory Council for Nursing Education and Practice. Ms. Prows is a member of the American Academy of Nursing and has received awards of recognition for her work in genetics education and research by the International Society of Nurses in Genetics, the National Coalition for Health Professional Education in Genetics, the Beta Iota Chapter of Sigma Theta Tau International, and Mount Saint Joseph’s School of Nursing.


With each passing year genomic technology and information increases in relevance for clinical practice in diverse healthcare settings. This article focuses on three examples of how genomics is impacting the care of patients in diverse healthcare settings: genomics and infectious diseases, genomics and breast cancer, and genomics and medications. Nurses have an important role in both helping patients understand the purpose, limitations, and potential benefits and risks of genomic technology and providing information related to their care.

Key words: cancer, drug response, genetic test, infectious disease, nursing

With each passing year genomics technology and information has increased...At the dawn of this century, the influence of genomics on healthcare was becoming apparent. With each passing year genomics technology and information has increased, and will continue to increase in relevance for clinical practice in diverse healthcare settings. Genomics is the study of the function and interaction of multiple genes, as well as environmental and psychosocial factors that contribute to the development and course of common conditions (Guttmacher & Collins, 2002). This article will provide an overview of genomics developments that are currently relevant to patient care: genomics and infectious diseases, genomics and breast cancer, and genomics and medications. Ways in which nurses can improve patients’ experiences within a healthcare environment that will become increasingly reliant on genomics technology and information will also be discussed.

Genomics and Infectious Diseases: HIV as an Exemplar

Virtually all nurses have cared for patients with human immunodeficiency virus (HIV) or have at least learned about the disease in school, continuing education programs, or Universal Precautions mandatory training. However, nurses are less likely to be aware of the ways that genomic technology is used in the diagnosis and treatment of HIV infection. This section will address the use of genomic technology in the diagnosis and treatment of HIV infections.

HIV infection is the result of interactions between the human host genome and the pathogen (HIV) genome. Specifically, HIV must enter host cells where it releases its genome, integrates into the host genome, and uses various host cell components to replicate its genome, construct new viral components, and assemble new functional particles before leaving the cell and infecting other host cells (Marsh & Helenius, 2006). HIV enters T cells and macrophages by interacting with naturally occurring cytokine receptors and chemokine co-receptors found in the host cell membrane. There are many different strains of HIV, each with a slightly different genome. All strains of HIV do not enter cells through the same receptor/co-receptor pair. Instead an HIV strain must match up with a particular receptor/co-receptor pair. Human T cells and macrophages have many different, naturally occurring cytokine receptors and chemokine co-receptors along their cell membranes. Different receptors are made up of different protein combinations as are different co-receptors. Each protein is encoded by a different gene. If one of those genes has a mutation that changes the structure, amount, or function of its protein, the function of the receptor or co-receptor to which it belongs may be compromised. This, in turn may cause a particular HIV strain’s entryway into a T-cell or macrophage to become impenetrable. An HIV strain that cannot enter a cell does not have access to the host genome and cannot replicate. This is one way in which the human host’s genetic factors influence the rate of infection (McNicholl, Smith, Qari, & Hodge, 1997).

During the early years of the acquired immune deficiency disease (AIDS) epidemic it was noted that some individuals did not become infected, despite repeated exposure to HIV through unprotected sexual contact. HIV type 1, which predominates during the early stage of infection, requires an entryway into the cell called CD4 together with its co-receptor, CCR5 (Cohen & Fauci, 2001). In 1996, some of the people who seemed to have an innate protection against HIV were found to have a portion of each of their CCR5 genes missing. Specifically, each CCR5 gene was missing 32 chemical bases from the same location within each gene. The deletion (loss of a piece of DNA from a chromosome) of this 32 ‘base pair’ (two bases which form a ‘rung of the DNA ladder’) (called delta32) prevents the production of its full length CCR5 protein. The CCR5 delta32 allele (a variant form of the gene) is present in up to 10% – 15% of Caucasians and 2% of African Americans, but virtually absent in native East Asians and Africans (Pacheco, 2002). People who have one CCR5 delta32 allele and one fully functional CCR5 allele (heterozygotes) will still produce the receptor but in reduced quantities. These people typically have slower progression to AIDS. People who have two CCR5 delta32 alleles (homozygotes) in each of their cells do not produce functional CCR5 receptors – the entryway for most forms of HIV-1. Without a way into the cell, HIV cannot infect its host. Yet, the lack of functional CCR5 receptors seems to have no ill effect on humans. (Carrington, Dean, Martin, & O'Brien, 1999; Doms & Peiper, 1997; McNicholl et al., 1997).

Once it became apparent that most forms of HIV-1 require CCR5 to infect the cell, scientists began efforts to develop HIV co-receptor antagonists as antiretroviral drugs. At the time of this writing, several candidate drugs were in Phase II and Phase III clinical trials. Several specifically target the CCR5 receptor by inhibiting its function or binding to CCR5 to block HIV entry. One such HIV entry inhibitor, maraviroc, was recommended for approval in April, 2007 by the Antiviral Advisory Committee of the FDA (Este & Telenti, 2007).

HIV-1 is highly mutable and strains have been reported that are able to enter the cell through other cell receptors, explaining how an individual homozygous for CCR5 delta32 allele can eventually become infected after repeated exposure to the HIV-1 pathogen (Cunningham et al., 2000; Doms & Peiper, 1997). The high mutation rate of HIV-1 is also a factor in the effectiveness of available antiretroviral drugs. Spontaneous mutations occur as the HIV-1 replicates within cells. These mutated strains may or may not be able to survive and further replicate. Those that survive within a given antiretroviral drug environment are referred to as resistant strains for the particular drug or combination of drugs.

Recently, drug-resistant HIV mutations have been detected in about 25% of infected patients who have not yet started on medication. Recently, drug-resistant HIV mutations have been detected in about 25% of infected patients who have not yet started on medication. Based on this finding, it is recommended that all people newly infected with HIV have antiretroviral resistance testing prior to selecting and starting their treatment regimen (Kirton, Kurtyka, & Sterken, 2007; Vicenti, Razzolini, Saladini, Romano, & Zazzi, 2007). There are two types of resistance assays: genotypic and phenotypic. Both are performed on HIV-1 extracted from a patient’s plasma. The genotypic assay compares the DNA sequence extracted from the virus against a laboratory control. Any mutations found in the patient’s virus are then compared against a regularly updated database. It usually takes 1 – 2 weeks to get results. The phenotypic assay is similar to a blood culture and sensitivity for antibiotic selection. The extracted virus is placed in various cultures with different antivirals and different concentrations of the antivirals. These assays can take several weeks before achieving reportable results. For the genotypic or phenotypic assay to be informative, at least 20 – 30% of the mutant HIV strains in a person must be resistant (Kirton et al., 2007).

Another type of pre-treatment molecular genetic testing receiving attention is one that identifies patients who are at high risk for developing a hypersensitivity reaction (sometimes referred to as multi-system inflammatory syndrome) to the nucleoside reverse transcriptase inhibitor, abacavir. The drug can be prescribed as a stand-alone medication or as part of a combination regimen. When individuals experience two symptoms associated with hypersensitivity (fever, rash, nausea, vomiting, headache, respiratory and gastrointestinal symptoms, lethargy, myalgia, or arthralgia) within six weeks of treatment that resolve 72 hours after stopping the medication, the patients are advised not to take abacavir again, since a second hypersensitivity reaction can be life-threatening. The hypersensitivity reaction has shown strong association with human leukocyte antigen (HLA) B*5701 of the major histocompatibility complex in Caucasian and Hispanic ethnic groups. A genetic test for HLA-B*5701 is commercially available. A significant reduction in the incidence of abacavir hypersensitivity reaction has been demonstrated since routinely offering the test in Western Australia and the UK. The genetic test results are recorded in the allergy field of the pharmacy system database within Western Australia so that patients found to be at high risk for abacavir hypersensitivity can avoid abacavir and, instead, be treated with other medications (Cressey & Lallemant, 2007; Lucas, Nolan, & Mallal, 2007).

Genomics and Oncology: Breast Cancer as an Exemplar

Nursing leaders in [oncology] have developed position statements [on] nurses’ roles in cancer genetics and have published genomics competencies for oncology advanced practice nurses.In no other specialty area has genomics had a greater impact than in oncology. Genomic discoveries are being translated throughout the continuum of cancer care (Jenkins, 2004). Nursing leaders in the field have developed position statements that address nurses’ roles in cancer genetics  (Oncology Nursing Society, 2000a, 2000b) and have published genomics competencies for oncology advanced practice nurses (Calzone, Jenkins, & Masny, 2002). This section provides an example of how oncology nurses are using genomics when providing patient care.

Case Scenario

TM (not a real patient) is a 29 year old woman who has a 40 year old sister recently diagnosed with breast cancer. Their mother died from ovarian cancer at 48 years of age. Their 65 year old maternal aunt had breast cancer in her right breast when she was 43 and a second primary breast cancer in her left breast when she was 50. TM and her sister discussed this family history with an advanced practice nurse (APN) in cancer genetics. The APN discussed the availability of BRCA1 and BRCA2 testing. TM wanted the test to decide whether or not she should have prophylactic bilateral mastectomy and oopherectomy. She also wanted the results to help her decide about having another child. TM’s sister agreed to have BRCA1/BRCA2 testing to determine if the "female cancer that has attacked our family" is related to a mutation in either of these genes. The APN explained that TM's sister's results were essential to determine whether or not the genetic test would be informative for TM and other at -risk family members. This is because BRCA1 and BRCA2 are just two of the several genes in which inherited mutations have been found in familial breast cancer. If TM’s sister’s BRCA1 and BRCA2 test results indicate she does not have a disease-associated mutation in either pair of genes, it is still possible that she has an inherited mutation in one or more different genes. In this situation, the BRCA1 and BRCA2 test will not be helpful for at-risk family members.  However, if a mutation associated with cancer predisposition is found in one of TM's sister’s BRCA1 or BRCA2 genes, the test results are informative and the specific mutation can be looked for in TM and other asymptomatic, at-risk family members.

Clinical application of genomics has been particularly evident in the area of breast cancer. As described in the case scenario in which there is a strong family history of breast and ovarian cancer, BRCA1/BRCA2 testing is available to identify whether or not at-risk family members have inherited a predisposition, cancer-associated mutation in the BRCA1 or BRCA2 genes (Roesser, 2003). People at risk for the inherited predisposition form of breast/ovarian cancer now have the opportunity (or burden) to decide about testing. Those found to be a carrier of a predisposition gene mutation, will have the opportunity to make informed decisions about early monitoring strategies and prophylactic treatments (d'Agincourt-Canning, 2006; Ray, Loescher, & Brewer, 2005; Van Riper & McKinnon, 2004). It should be noted, that BRCA1/BRCA2 testing will not identify all inherited forms of breast cancer and therefore, a strong family history alone is consistent with a diagnosis of hereditary predisposition to breast/ovarian cancer (Tranin, 2006).

It has been recommended that all nurses be able to obtain a three-generation family history and identify patients and/or their family members who may benefit from specific genetic and genomic information and/or services...It has been recommended that all nurses be able to obtain a three-generation family history and identify patients and/or their family members who may benefit from specific genetic and genomic information and/or services based on assessment data. (Consensus Panel, 2006). Nurses who do not have specialty training in genetics and cancer genetics counseling are not expected to provide all the necessary information patients need to make an informed decision about whether or not to undergo BRCA1/BRCA2 testing (Chapman, 2007). However, any nurse who cares for these patients or who is approached by healthy women who have questions about BRCA1/BRCA2 testing needs to know how to locate healthcare professionals trained in genetics or cancer genetics (Tranin, Masny, & Jenkins, 2003).

Returning to the case example, TM wanted the BRCA1/BRCA2 test to decide whether or not she should have prophylactic bilateral mastectomy and oopherectomy. These are two risk-reduction options available for asymptomatic women who are BRCA1/BRCA2 mutation carriers. In addition, chemoprevention options may be considered. Early and frequent surveillance is also recommended for BRCA1/BRCA2 mutation carriers to improve the chance of detecting and successfully treating early stage breast or ovarian cancer (Bast et al., 2007; Bermejo-Perez, Marquez-Calderon, & Llanos-Mendez, 2007; NCCN, 2007; Nusbaum & Isaacs, 2007; Roukos & Briasoulis, 2007).

Approximately 90% of patients with breast cancer do not have an inherited form of the disease (Rieger, 2004). Yet, even for these patients, genetic testing may be used. One such genetic test that has been recommended for all women who are diagnosed with breast cancer analyzes tumor cells for a gene called human epidermal growth factor receptor 2 (HER2). When cells have an overabundance of HER2 genes, they also have over expression of the genes’ products (receptors). Excess HER2 receptors result in increased signaling, cell proliferation, and malignant growth. Trastuzumab (HerceptinÒ) is a monoclonal antibody that specifically targets and blocks HER2 receptors. Randomized clinical trials have demonstrated significant improvement in disease-free survival and overall survival in women who receive adjuvant trastuzumab during and/or after traditional chemotherapy with early stage breast cancer and evidence of HER2 over expression. (Chorn, 2006). Because trastuzumab is target specific, it is only therapeutic if HER2 over expression is present. Therefore, guidelines regarding this testing and subsequent use of trastuzumab have been developed (Wolff et al., 2007). Patients with breast cancer might also have a genetic test called OncoTypeDX. This test analyzes node-negative, estrogen-receptor-positive, early-stage breast cancer cells for the activity of 16 genes to assess recurrence risk and help clinicians select chemotherapy accordingly (Chapman, 2007). These types of tumor specific genetic tests are relevant not only for women with sporadic breast cancer but also for women who have a BRCA1 or BRCA2 mutation and develop breast cancer.

Genomics and Medications: Food and Drug Administration’s Labeling Initiative as an Exemplar

Within the last five years, the Food and Drug Administration (FDA) has taken an active role in promoting clinical consideration of genes involved in patient response to certain medications (Lesko & Woodcock, 2004). At the time of this writing, about ten percent of drug labels approved by the FDA contained information about genes or gene products or both that influence medication efficacy and/or toxicity (Food and Drug Administration, 2006). In this section two medications and the genetic information contained within the labeling information will be highlighted: atomoxetine and warfarin.


Atomoxetine is a non-stimulant medication for treatment of attention-deficit/hyperactivity disorder (ADHD). As with other psychotropics, the effectiveness and experiences with toxicity vary considerably between patients treated with atomoxetine (Michelson et al., 2007). One source of response variability is related to the rate of atomoxetine metabolism which is heavily influenced by an isoenzyme called cytochrome P450 CYP2D6 (Sauer et al., 2003).

The CYP2D6 gene has been studied for about 20 years (Gonzalez et al., 1988). The most common CYP2D6 variants that do not produce functional enzyme or produce deficient enzyme activity have been identified in people throughout the world. People who have two CYP2D6 variant alleles that are unable to produce functional enzyme are genetically predisposed to a poor metabolizer (PM) phenotype while those who have CYP2D6 variant alleles that produce deficient enzyme are predisposed to an intermediate metabolizer (IM) phenotype. People who have two CYP2D6 genes that produce full functioning enzyme are genetically predisposed to have an extensive metabolizer (EM) phenotype (also known as normal phenotype). Some people have more than two copies of normally functioning CYP2D6 genes and thus produce excessive amounts of the enzyme. They are genetically predisposed to have an ultra-rapid metabolizer (UM) phenotype (Bathum, Johansson, Ingelman-Sundberg, Horder, & Brosen, 1998; Bradford, 2002; Cai, Chen, & Zhang, 2007; Lovlie, Daly, Molven, Idle, & Steen, 1996; McLellan, Oscarson, Seidegard, Evans, & Ingelman-Sundberg, 1997; Mendoza et al., 2001; Sachse, Brockmoller, Bauer, & Roots, 1997; Sistonen et al., 2007).

There are several different enzymes involved in the metabolism of atomoxetine so despite the absence of CYP2D6 enzyme in people with PM phenotype the medication is still broken down to its various metabolites and primarily eliminated through the urine (Sauer et al., 2003). However, the rate of metabolism and thus elimination is slower in patients with a CYP2D6 PM phenotype. In these patients, the mean peak plasma concentrations of atomoxetine have been measured at five-fold higher concentrations when compared to those with EM phenotypes (Michelson et al., 2007).

The FDA approved drug label states within the “laboratory test” section that “laboratory tests are available to identify CYP2D6 PMs.”  The “adverse reactions” portion of the label indicates that PM patients are more likely to experience decreased appetite, insomnia, sedation, depression, tremor, early morning awakening, pruritus, and mydriasis (Eli Lilly, 2007).

Since the creation of this label, there is evidence that atomoxetine is more effective (p = 0.002) in people with CYP2D6 genotypes consistent with PM phenotype than those with predicted EM phenotype. Michelson et al., 2007 demonstrated that children with CYP2D6 predicted EM phenotype were more likely to discontinue their therapy due to lack of efficacy than those with CYP2D6 predicted PM phenotype. However, there was a trend for more discontinuations due to adverse drug reactions (ADRs) in PMs when compared to EMs (p=0.063). Based on these study results clinicians may be uncertain about how to use CYP2D6 test results when prescribing atomoxetine. Further prospective studies are needed to determine dosage strategies based on CYP2D6 test results that maximize time to efficacy while minimizing ADRs.


Warfarin is an anticoagulant used since 1955 (Wittkowsky, 2003) to prevent or treat venous thrombosis, pulmonary embolism, or thromboembolism. It has been listed as the second most frequent medication implicated in adverse events that result in emergency department visits (Budnitz et al., 2006). Warfarin’s effectiveness is dependent on maintaining a prothrombin time ratio, reported as International Normalized Ratio (INR), within a narrow therapeutic range. INRs between 2 and 3 are targeted for most anticoagulation indications (Hirsh, Fuster, Ansell, & Halperin, 2003). The weekly maintenance dose to achieve this target range for some patients may be as low as 10 mg /week yet for other patients it may be as high as 80 mg/week (Reynolds, Valdes, Hartung, & Linder, 2007). INRs below 2 have been associated with a 17-fold increase risk in stroke whereas INRs above 4.5 have been associated with a five-fold increase risk in intracranial hemorrhage (Ansell, 2003).

The Bristol-Myers Squibb Company’s Medication Guide for warfarin (Bristol-Myers Squibb Company, 2006) highlights for patients the many factors that can change warfarin’s effectiveness and bleeding risk. Among the factors that patients can control are changes in diet, use of herbal or vitamin supplements, and changes in prescription and over-the-counter medications. Additional factors that prescribers have needed to consider when dosing warfarin are age, gender, weight, and health status.

Since August 16, 2007, when the FDA announced the addition of genetic information within the warfarin label (Riley, 2007), prescribers may be struggling with whether or not to also factor in a patient’s genotype for two genes associated with variation in warfarin response. The genes are CYP2C9 and vitamin K epoxide reductase complex subunit 1 (VKORC1). CYP2C9 codes for an isoenzyme (CYP2C9) within the cytochrome P450 enzyme group. The isoenzyme is responsible for metabolizing S-warfarin, which is the more active component of warfarin. Similar to what was described for CYP2D6 in the atomoxetine example, people who have two CYP2C9 variant genes that are unable to produce functional enzyme are genetically predisposed to a PM phenotype and those who have a variant and a wild type CYP2C9 gene are predisposed to deficient enzyme activity and IM phenotype. The potential consequences of impaired metabolism of the most potent anticoagulation component of warfarin are slower elimination and longer half life of warfarin and therefore a greater tendency toward bleeding. Such patients may have a lower maintenance dose requirement (Aithal, Day, Kesteven, & Daly, 1999). Warfarin works by inhibiting vitamin K epoxide reductase multiprotein complex (VKOR) that is essential for the eventual production of coagulation factors II, VII, IX, X. VKORC1 produces a protein that is part of VKOR (Loebstein et al., 2005; Rost et al., 2004). Five common VKORC1 variants associated with warfarin sensitivity (less warfarin dose requirement) have been described (Wadelius et al., 2005).

The revised warfarin label discusses CYP2C9 and VKORC1 variant alleles associated with variability in dose requirement in the “Clinical Pharmacology,” “Precautions,” and “Dosing” sections. Genetic testing is not recommended nor is its availability directly discussed as in the atomoxetine label. However, within the “Dosing” section of the revised Warfarin label, it does state, “The lower initiation doses should be considered for patients with certain genetic variations in CYP2C9 and VKORC1 enzymes…” (Bristol-Myers Squibb Company, 2007, p. 25). A brief summary of these changes, framed within a red border, was added to the National Library of Medicine’s consumer targeted Medline Plus (2007) Drug Information website September 1, 2007. Later in September, 2007, the FDA cleared a warfarin pharmacogenetic test (Nanosphere, 2008, Riley, 2007) that analyzes a patient’s DNA for two CYP2C9 variant alleles and one VKORC1 variant allele. The alleles analyzed in the test together with routinely considered clinical factors, such as age, weight, and height, have been shown to account for 50% - 60% of the variability in warfarin stable dose requirement (Caldwell et al., 2007; Sconce et al., 2005). Prospective clinical studies (Table 1) to determine the clinical utility and safety of dosing algorithms that include genetic and clinical information are underway. Depending on the results of these studies, genetic testing during the warfarin dosing initiation period may become common.

Nurses should expect that even in the future, if a genetic test is able to affordably analyze all genes and their variants known to influence the variability in a patient’s response to warfarin, the other clinical and environmental factors that are considered today when initiating and adjusting warfarin doses will still need to be considered. Furthermore, INRs will continue to be critical for monitoring a patient’s response to warfarin as long as the patient is taking the medication.

Implications for Nursing Practice

With the exception of the BRCA1/BRCA2 testing example, this paper has focused on genetic testing that is performed at the point of care for diagnostic or medication selection or dosing purposes. This point-of-care testing will infiltrate the practice of many nurses and the implications for their practice are discussed below.

Point-of-Care Counseling

...when genetic testing to predict drug response becomes more common, nurses will have an important role in helping patients understand the purpose, limitations, and potential benefits and risks of such testing. Predisposition genetic counseling for diseases or disorders is provided by professionals trained in genetics. During the counseling sessions, comprehensive information is presented in a nondirective manner to enable the patient to make an informed decision about whether or not to have the predisposition test. This type of counseling by a professional trained in genetics, however, is not practical when the genetic test is being used to identify a predisposition for unintended drug responses for a medication that needs to be initiated by the prescriber at or shortly after the time of evaluation. Instead, prescribers will need to be able to explain the purpose, limitations, and potential benefits and risks of such testing at the point of care. This information is presented in Table 2 which drew on the work of Breckenridge et al. (2004), Marx-Stolting (2007), and Morley and Hall (2004). Prescribers will also need to be able to explain how the test results, together with other clinical data, influence treatment decisions (Breckenridge et al.; Marx-Stolting; Morley & Hall).

In addition all nurses will need to be aware of the purpose, limitations, and potential benefits and risks of such testing at the point of care because teaching patients about a medication’s purpose, potential side effects, and any administration considerations is an important responsibility of nurses (Ekman, Schaufelberger, Kjellgren, Swedberg, & Granger, 2007; Hegney, Plank, Watson, Raith, & McKeon, 2005; King, 2004; Viale & Sanchez Yamamoto, 2004). This is especially true for warfarin (Lamarche & Heale, 2007; Newall, Johnston, & Monagle, 2006; Scalley, Kearney, & Jakobs, 1979). It then makes sense that when genetic testing to predict drug response becomes more common, nurses will have an important role in helping patients understand the purpose, limitations, and potential benefits and risks of such testing. As with any type of testing or procedure, patients will have the right to refuse the testing or procedure after receiving the information. Patients that do have such testing will need information about how their genetic test results influence their immediate plan of care and how these results might also be relevant for future care.

Counseling Related to Direct-to-Consumer Genetics Testing Products

...purchasing tests that analyze multiple genes, simply because the bulk rate seems more cost effective, is not wise. Explaining genetic information related to testing may be difficult for nurses and physicians as their knowledge about genetics and genetics testing is limited (Baars, Henneman, & Ten Kate, 2005; Harvey et al., 2007; Maradiegue, Edwards, Seibert, Macri, & Sitzer, 2005). However, advanced practice nurses with prescribing privileges will need knowledge about the availability and clinical utility of genetic tests that may be relevant for the medications they commonly prescribe. They will need to know the situations in which such a test might be relevant, the type of results that are possible from the test, and the implications of those test results for the management of a patient’s care.

Additionally, all nurses need to help patients evaluate information about these and other genetic tests that are marketed directly to consumers via the Internet or other forms of media. The increasing number of companies touting genetic tests for purposes such as helping people select the right nutritional supplement or choose the best skin cream provided incentive for the Federal Trade Commission (2006) to distribute a warning of the dubious nature of such claims. In addition, some companies might offer a discount for a clinically relevant test if the consumer also buys additional genetic tests. Yet, the results of the additional tests may or may not ever be relevant to their healthcare management throughout their remaining lifetime. Therefore, it is important to warn consumers that purchasing tests that analyze multiple genes, simply because the bulk rate seems more cost effective, is not wise. As noted in Table 2, people who are considered to have wild type alleles by default, because the specific variants analyzed by the test were not detected, will likely need to be retested if results for such a test become relevant for future treatment decisions.  Nurses can play an important role in consumer protection by encouraging consumers to contact a professional trained in genetics before purchasing one of the growing numbers of genetic tests marketed on the Internet.


...all nurses need to help patients evaluate information about... genetic tests that are marketed directly to consumers... Nurses in all healthcare settings are likely to encounter patients whose care involves the consideration of genomic information and access to genomic technology. This article provided examples of recent genomic developments that are relevant for clinical practice in diverse healthcare settings. As patient teaching is an essential nursing responsibility in virtually every healthcare setting, nurses need to become conversant in the purpose, limitations, and potential benefits and risks of genomic information and technology that is relevant for their patient population.


Table 1: Clinical trials for pharmacogenetic-based warfarin dosing

PRospective Evaluation Comparing Initiation of Warfarin StrategiEs (PRECISE): Pharmacogenetic-Guided Versus Usual Care

A Pharmacogenetic Study of Warfarin Dosing, "The COUMA-GEN Study"

Comparison of Warfarin Dosing Using Decision Model vs. Pharmacogenetic Algorithm

Modeling Genotype and Other Factors to Enhance the Safety of Coumadin Prescribing

CReating an Optimal Warfarin Nomogram (CROWN) Trial


Table 2: Purpose, limitations, and potential benefits and risks of pharmacogenetic testing


To help prescribers select an effective medication to treat a patient’s condition and to determine a safe dose without compromising time to efficacy


Current tests analyze the most common variants within a gene that are associated with delayed/diminished efficacy or adverse drug reactions due to toxicity. Even if results indicate variants were not detected, it is still possible the patient possesses one or more rare variants that influence drug response. Drug response is influenced by many non-genetic factors as discussed in the warfarin example.


Maximize efficacy and minimize the likelihood of toxicity for the medication(s) being considered for a patient’s treatment. Because the genes we inherit do not change, the same genetic test will not need to be repeated if variants are detected. However, as technology improves so that all base pairs within a gene can be analyzed at low cost, a previously tested gene may be reanalyzed if no variants had previously been detected.


Test results may have implications for disease/disorder risks that were not known at the time of the test but once documented in the medical records could be a source for genetic discrimination by health or life insurers or employers. In situations where medication options are limited, pharmacogenetic testing may result in drug orphans – those who have gene variants that prevent them from achieving efficacy from a medication. However, without testing, such patients would eventually be identified due to lack of efficacy but only after having been placed unnecessarily on a medication for an extended period.



Cynthia A. Prows, MSN, CNS, FAAN 

Ms. Prows received her BSN and MSN from the University of Cincinnati College of Nursing. In 1990 she became a clinical nurse specialist in genetics; since that time she has published over 20 articles about genetics in peer reviewed nursing and medical journals. She directs the Genetics Education Program for Nurses which provides web-based genetics continuing education opportunities for nurses as well as web-based instructional resources for nursing faculty. Ms. Prows recently completed a four year appointment with the Health Resources and Services Administration’s National Advisory Council for Nursing Education and Practice. Ms. Prows is a member of the American Academy of Nursing and has received awards of recognition for her work in genetics education and research by the International Society of Nurses in Genetics, the National Coalition for Health Professional Education in Genetics, the Beta Iota Chapter of Sigma Theta Tau International, and Mount Saint Joseph’s School of Nursing.

© 2008 OJIN: The Online Journal of Issues in Nursing
Article published January 31, 2008


Aithal, G. P., Day, C. P., Kesteven, P. J., & Daly, A. K. (1999). Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet, 353(9154), 717-719.

Ansell, J. E. (2003). Optimizing the efficacy and safety of oral anticoagulant therapy: High-quality dose management, anticoagulation clinics, and patient self-management. Seminars in Vascular Medicine, 3(3), 261-270.

Baars, M. J., Henneman, L., & Ten Kate, L. P. (2005). Deficiency of knowledge of genetics and genetic tests among general practitioners, gynecologists, and pediatricians: A global problem. Genetics in Medicine, 7(9), 605-610.

Bast, R. C., Jr., Brewer, M., Zou, C., Hernandez, M. A., Daley, M., Ozols, R., et al. (2007). Prevention and early detection of ovarian cancer: Mission impossible? Recent Results in Cancer Research, 174, 91-100.

Bathum, L., Johansson, I., Ingelman-Sundberg, M., Horder, M., & Brosen, K. (1998). Ultrarapid metabolism of sparteine: frequency of alleles with duplicated CYP2D6 genes in a Danish population as determined by restriction fragment length polymorphism and long polymerase chain reaction. Pharmacogenetics, 8(2), 119-123.

Bermejo-Perez, M. J., Marquez-Calderon, S., & Llanos-Mendez, A. (2007). Effectiveness of preventive interventions in BRCA1/2 gene mutation carriers: a systematic review. International Journal of Cancer, 121(2), 225-231.

Bradford, L. D. (2002). CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics, 3(2), 229-243.

Breckenridge, A., Lindpaintner, K., Lipton, P., McLeod, H., Rothstein, M., & Wallace, H. (2004). Pharmacogenetics: Ethical problems and solutions. Nature Reviews Genetics, 5(9), 676-680.

Bristol-Myers Squibb Company. (2006, April 2006). Medication Guide: Coumadin (COU-ma-din) tablets, (warfarin sodium tablets, USP) crystalline. Retrieved October 11, 2007, from

Bristol-Myers Squibb Company. (2007, August 2007). Coumadin tablets, (warfarin sodium tablets, USP) crystalline; Coumadin for injection (warfarin sodium for injection, USP).  Retrieved October 22, 2007, from

Budnitz, D. S., Pollock, D. A., Weidenbach, K. N., Mendelsohn, A. B., Schroeder, T. J., & Annest, J. L. (2006). National surveillance of emergency department visits for outpatient adverse drug events. Journal of the American Medical Association, 296(15), 1858-1866.

Cai, W. M., Chen, B., & Zhang, W. X. (2007). Frequency of CYP2D6*10 and *14 alleles and their influence on the metabolic activity of CYP2D6 in a healthy Chinese population. Clinical Pharmacology and Therapeutics, 81(1), 95-98.

Caldwell, M. D., Berg, R. L., Zhang, K. Q., Glurich, I., Schmelzer, J. R., Yale, S. H., et al. (2007). Evaluation of genetic factors for warfarin dose prediction. Clinical Medicine and Research, 5(1), 8-16.

Calzone, K. A., Jenkins, J., & Masny, A. (2002). Core competencies in cancer genetics for advanced practice oncology nurses. Oncology Nursing Forum, 29(9), 1327-1333.

Carrington, M., Dean, M., Martin, M. P., & O'Brien, S. J. (1999). Genetics of HIV-1 infection: Chemokine receptor CCR5 polymorphism and its consequences. Human Molecular Genetics, 8(10), 1939-1945.

Chapman, D. D. (2007). Cancer genetics. Seminars in Oncology Nursing, 23(1), 2-9.

Chorn, N. (2006). Accurate identification of HER2-positive patients is essential for superior outcomes with trastuzumab therapy. Oncology Nursing Forum, 33(2), 265-272.

Cohen, O. J., & Fauci, A. S. (2001). Pathogenesis and medical aspects of HIV-1 infection. In D. M. Knipe, P. M. Howley, D. E. Griffin, R. A. Lamb, M. A. Martin, B. Roizman & S. E. Straus (Eds.), Fields Virology (Fourth ed., Vol. 2, pp. 2043-2094). Philadelphia: Lippincott Williams & Wilkins.

Consensus Panel on Genetic/Genomic Nursing Competencies. (2006). Essential nursing competencies and curricula guidelines for genetics and genomics. Silver Spring, MD: American Nurses Association.

Cressey, T. R., & Lallemant, M. (2007). Pharmacogenetics of antiretroviral drugs for the treatment of HIV-infected patients: An update. Infections, Genetics and Evolution, 7(2), 333-342.

Cunningham, A. L., Li, S., Juarez, J., Lynch, G., Alali, M., & Naif, H. (2000). The level of HIV infection of macrophages is determined by interaction of viral and host cell genotypes. Journal of Leukocyte Biology, 68(3), 311-317.

d'Agincourt-Canning, L. (2006). A gift or a yoke? Women's and men's responses to genetic risk information from BRCA1 and BRCA2 testing. Clinical Genetics, 70(6), 462-472.

Doms, R. W., & Peiper, S. C. (1997). Unwelcomed guests with master keys: How HIV uses chemokine receptors for cellular entry. Virology, 235(2), 179-190.

Ekman, I., Schaufelberger, M., Kjellgren, K. I., Swedberg, K., & Granger, B. B. (2007). Standard medication information is not enough: Poor concordance of patient and nurse perceptions. Journal of Advanced Nursing, 60(2), 181-186.

Eli Lilly & Company. (2007). Strattera®. Retrieved October 18, 2007 from:

Este, J. A., & Telenti, A. (2007). HIV entry inhibitors. Lancet, 370(9581), 81-88.

Federal Trade Commission. (2006). Facts for consumers. At-home genetic tests: A healthy dose of skepticism may be the best prescription. Retrieved October 22, 2007 from:

Food and Drug Administration. (2006). Table of valid genomic biomarkers in the context of approved drug labels. Retrieved September 19, 2007 from:

Gonzalez, F. J., Skoda, R. C., Kimura, S., Umeno, M., Zanger, U. M., Nebert, D. W., et al. (1988). Characterization of the common genetic defect in humans deficient in debrisoquine metabolism. Nature, 331(6155), 442-446.

Guttmacher, A. E., & Collins, F. S. (2002). Genomic medicine - A primer. New England Journal of Medicine, 347(19), 1512-1520.

Harvey, E. K., Fogel, C. E., Peyrot, M., Christensen, K. D., Terry, S. F., & McInerney, J. D. (2007). Providers' knowledge of genetics: A survey of 5915 individuals and families with genetic conditions. Genetics in Medicine, 9(5), 259-267.

Hegney, D., Plank, A., Watson, J., Raith, L., & McKeon, C. (2005). Patient education and consumer medicine information: A study of provision by Queensland rural and remote area Registered Nurses. Journal of Clinical Nursing, 14(7), 855-862.

Hirsh, J., Fuster, V., Ansell, J., & Halperin, J. L. (2003). American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation, 107(12), 1692-1711.

Jenkins, J. (2004). Genomics: Offering hope for oncology care. Seminars in Oncology Nursing, 20(3), 209-212.

King, R. L. (2004). Nurses' perceptions of their pharmacology educational needs. Journal of Advanced Nursing, 45(4), 392-400.

Kirton, C. A., Kurtyka, D., & Sterken, D. J. (2007). New insights into HIV resistance testing: Nursing guidelines and implications. The Journal of the Association of Nurses in AIDS Care, 18(3), 74-86.

Lamarche, K., & Heale, R. (2007). Communicating the safety essentials of oral anticoagulant therapy. Home Healthcare Nurse, 25(7), 448-456; quiz 457-448.

Lesko, L. J., & Woodcock, J. (2004). Opinion. Translation of pharmacogenomics and pharmacogenetics: A regulatory perspective. Nature Reviews Drug Discovery, 3(9), 763-769.

Loebstein, R., Vecsler, M., Kurnik, D., Austerweil, N., Gak, E., Halkin, H., et al. (2005). Common genetic variants of microsomal epoxide hydrolase affect warfarin dose requirements beyond the effect of cytochrome P450 2C9. Clinical Pharmacology and Therapeutics, 77(5), 365-372.

Lovlie, R., Daly, A. K., Molven, A., Idle, J. R., & Steen, V. M. (1996). Ultrarapid metabolizers of debrisoquine: Characterization and PCR-based detection of alleles with duplication of the CYP2D6 gene. FEBS Letters, 392(1), 30-34.

Lucas, A., Nolan, D., & Mallal, S. (2007). HLA-B*5701 screening for susceptibility to abacavir hypersensitivity. The Journal of Antimicrobial Chemotherapy, 59(4), 591-593.

Maradiegue, A., Edwards, Q. T., Seibert, D., Macri, C., & Sitzer, L. (2005). Knowledge, perceptions, and attitudes of advanced practice nursing students regarding medical genetics. Journal of the American Academy of Nurse Practitioners, 17(11), 472-479.

Marsh, M., & Helenius, A. (2006). Virus entry: Open sesame. Cell, 124(4), 729-740.

Marx-Stolting, L. (2007). Pharmacogenetics and ethical considerations: Why care? Pharmacogenomics Journal, 7(5), 293-296.

McLellan, R. A., Oscarson, M., Seidegard, J., Evans, D. A., & Ingelman-Sundberg, M. (1997). Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians. Pharmacogenetics, 7(3), 187-191.

McNicholl, J. M., Smith, D. K., Qari, S. H., & Hodge, T. (1997). Host genes and HIV: The role of the chemokine receptor gene CCR5 and its allele. Emerging Infectious Diseases, 3(3), 261-271.

Medline Plus. (2007). Warfarin. Retrieved October 22, 2007 from:

Mendoza, R., Wan, Y. J., Poland, R. E., Smith, M., Zheng, Y., Berman, N., et al. (2001). CYP2D6 polymorphism in a Mexican American population. Clinical Pharmacology and Therapeutics, 70(6), 552-560.

Michelson, D., Read, H. A., Ruff, D. D., Witcher, J., Zhang, S., & McCracken, J. (2007). CYP2D6 and clinical response to atomoxetine in children and adolescents with ADHD. Journal of the American Academy of Child and Adolescent Psychiatry, 46(2), 242-251.

Morley, K. I., & Hall, W. D. (2004). Using pharmacogenetics and pharmacogenomics in the treatment of psychiatric disorders: Some ethical and economic considerations. Journal of Molecular Medicine, 82(1), 21-30.

Nanosphere. Verigene® Warfarin metabolism nucleic acid test (IVD). (2008). Retrieved January 5, 2008 from:

NCCN. (2007). Hereditary breast and/or ovarian cancer. Practice Guidelines in Oncology   Retrieved December 10, 2007, from

Newall, F., Johnston, L., & Monagle, P. (2006). A survey of pediatric cardiology nurses' understanding of warfarin therapy. Pediatric Cardiology, 27(2), 204-208.

Nusbaum, R., & Isaacs, C. (2007). Management updates for women with a BRCA1 or BRCA2 mutation. Molecular Diagnosis & Therapy, 11(3), 133-144.

Oncology Nursing Society. (2000a). Cancer predisposition genetic testing and risk assessment counseling: Position statement. Oncology Nursing Forum, 27(9), 1.

Oncology Nursing Society. (2000b). The role of the oncology nurse in cancer genetic counseling: Position statement. Oncology Nursing Forum, 27(9), 1348.

Pacheco, A.G.F. (2002). CCR5 receptor gene and HIV infection. Retrieved November 4, 2007 from

Ray, J. A., Loescher, L. J., & Brewer, M. (2005). Risk-reduction surgery decisions in high-risk women seen for genetic counseling. Journal of Genetic Counseling, 14(6), 473-484.

Reynolds, K. K., Valdes, R., Jr., Hartung, B. R., & Linder, M. W. (2007). Individualizing warfarin therapy. Personalized Medicine, 4(1), 11-31.

Rieger, P. T. (2004). The biology of cancer genetics. Seminars in Oncology Nursing, 20(3), 145-154.

Riley, K. M. (2007, August 16, 2007). Transcript of FDA press conference on warfarin.  Retrieved October 19, 2007, from

Roesser, K. A. (2003). Understanding hereditary breast and ovarian cancer. Clinical Journal of Oncology Nursing, 7(5), 591-594.

Rost, S., Fregin, A., Ivaskevicius, V., Conzelmann, E., Hortnagel, K., Pelz, H. J., et al. (2004). Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature, 427(6974), 537-541.

Roukos, D. H., & Briasoulis, E. (2007). Individualized preventive and therapeutic management of hereditary breast ovarian cancer syndrome. Nature Clinical Practice Oncology, 4(10), 578-590.

Sachse, C., Brockmoller, J., Bauer, S., & Roots, I. (1997). Cytochrome P450 2D6 variants in a Caucasian population: Allele frequencies and phenotypic consequences. American Journal of Human Genetics, 60(2), 284-295.

Sauer, J. M., Ponsler, G. D., Mattiuz, E. L., Long, A. J., Witcher, J. W., Thomasson, H. R., et al. (2003). Disposition and metabolic fate of atomoxetine hydrochloride: The role of CYP2D6 in human disposition and metabolism. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 31(1), 98-107.

Scalley, R. D., Kearney, E., & Jakobs, E. (1979). Interdisciplinary inpatient warfarin education program. American Journal of Hospital Pharmacy, 36(2), 219-220.

Sconce, E. A., Khan, T. I., Wynne, H. A., Avery, P., Monkhouse, L., King, B. P., et al. (2005). The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: Proposal for a new dosing regimen. Blood, 106(7), 2329-2333.

Sistonen, J., Sajantila, A., Lao, O., Corander, J., Barbujani, G., & Fuselli, S. (2007). CYP2D6 worldwide genetic variation shows high frequency of altered activity variants and no continental structure. Pharmacogenetics and Genomics, 17(2), 93-101.

Tranin, A., Masny, A., & Jenkins, J. (2003). Genetics in oncology practice. Cancer risk assessment. Philadelphia: Oncology Nursing Society Press.

Tranin, A. S. (2006). The bridge from genomic discoveries to disease prevention. 2006 Oncology Nursing Society Clinical Lectureship. Oncology Nursing Forum, 33(5), 891-900.

Van Riper, M., & McKinnon, W. C. (2004). Genetic testing for breast and ovarian cancer susceptibility: A family experience. Journal of Midwifery and Women's Health, 49(3), 210-219.

Viale, P. H., & Sanchez Yamamoto, D. (2004). The attitudes and beliefs of oncology nurse practitioners regarding direct-to-consumer advertising of prescription medications. Oncology Nursing Forum, 31(4), 777-783.

Vicenti, I., Razzolini, F., Saladini, F., Romano, L., & Zazzi, M. (2007). Use of peripheral blood DNA for genotype antiretroviral resistance testing in drug-naive HIV-infected subjects. Clinical Infectious Diseases, 44(12), 1657-1661.

Wadelius, M., Chen, L. Y., Downes, K., Ghori, J., Hunt, S., Eriksson, N., et al. (2005). Common VKORC1 and GGCX polymorphisms associated with warfarin dose. Pharmacogenomics J, 5(4), 262-270.

Wittkowsky, A. K. (2003). Warfarin and other coumarin derivatives: Pharmacokinetics, pharmacodynamics, and drug interactions. Seminars in Vascular Medicine, 3(3), 221-230.

Wolff, A. C., Hammond, M. E., Schwartz, J. N., Hagerty, K. L., Allred, D. C., Cote, R. J., et al. (2007). American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Journal of Clinical Oncology, 25(1), 118-145.

Citation: Prows, C., (January 31, 2008)  "Clinical Aspects of Genomics: An Update" OJIN: The Online Journal of Issues in Nursing. Vol. 13 No. 1, Manuscript 2.