Genetics and Genomics in Oncology Nursing Practice

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Preface: Genetics and Genomics: The Evolution of Oncology Nursing

Agnes Masny, MSN, MPH, BS, RN, CRNP, and Jean Jenkins, PhD, RN, FAAN

Where We Have Been

Since its inception, the nursing profession has continually endeavored to evolve so that individuals and communities could benefit from the care, knowledge, and skills of practicing nurses (Ponte, 2004). Throughout the 20th century, nurses’ knowledge of genetics was influenced by the findings of Gregor Mendel, who, in 1865, described how heredity is transmitted. Mendel’s findings were followed by further genetic discoveries that shaped nursing practice and health care in general (see Figure 1). Many of these genetic discoveries influenced the understanding of single gene disorders, such as Huntington disease, but did not affect our understanding of the genetic mechanisms of common diseases.

The release of Genetics in Oncology Nursing: Cancer Risk Assessment (Tranin, Masny, & Jenkins, 2003) coincided with the completion of the Human Genome Project, and genetic discoveries have been on the fast track ever since. Our understanding of the impact of genes on health and disease has evolved beyond the notion of a single-gene approach to a genomic approach (e.g., multiple genes interacting with each other and with the environment). In the past, most nurses learned about genetic disorders caused by single genes. For example, sickle-cell disease is caused by a mutation in the beta globulin gene of hemoglobin (HBB). Clinical differences in patients with sickle-cell disease have long been observed with the severity of disease ranging from mild with long-term survival to severe with organ damage and early death (Genetics Home Reference, 2009). This clinical diversity in a single-gene disorder suggested that other differences affect the HBB mutation (Steinberg, 1996). With the mapping of the human genome (International Human Genome Sequencing Consortium, 2001; Venter et al., 2001), other genes that modify the HBB mutation have been identified, such as variations in coagulation genes and gene variations in specific populations (Kutlar, 2007). These newly discovered variations in other genes were found to interact with the HBB gene (gene-gene interactions) and accounted for the clinical differences in sickle-cell disease severity. The genomic discoveries in sickle-cell disease now are resulting in the identification of new diagnostic approaches and new targets for treatment. A genetic disorder once attributed to a single gene is now studied, diagnosed, and treated utilizing a genomic approach (i.e., looking at multiple genes and their interaction). This simplified summary example for one disease illustrates how the practice of genetics has evolved to genomics. Now, health professionals are elucidating the underlying genetic and genomic mechanisms for all diseases using the same genetic and genomic approach. This has resulted in the invariable evolution of nursing practice to meet the genetic and genomic healthcare needs of individuals, families, and communities.

Genetics and Genomics in Oncology

Cancer is a genetic disease at the level of the cell. Hematologic cancers, such as leukemia, have long been known to be caused by chromosomal abnormalities (Nowell & Hungerford, 1961). DNA replication errors were later suspected as the basis for solid tumors (Loeb, Springgate, & Battula, 1974). The 1970s through the early 1990s saw the field of cancer genetics evolving with breakthroughs such as

• Recognition of family constellations of cancers that fit hereditary patterns of transmission (Lynch et al., 1979)
• Study of genes infected by viruses leading to the discovery of genes that regulate human cell division (i.e., oncogenes and tumor suppressor genes) (Klein, 1988)
• Human Genome Project beginning in 1990 (National Human Genome Research Institute, 2009)
• Identification of the multiple genetic events needed to progress from normal colon mucosa to an adenoma to a colon cancer to a colon cancer with metastatic potential (Cho & Vogelstein, 1992)
• Discovery of the DNA sequence of the BRCA1 gene associated with hereditary breast and ovarian cancer (Miki et al., 1994)
• Cancer therapies developed to stop cell growth: Radiation therapy caused DNA strand breaks (Olive, 1998), and chemotherapy irreparably damaged newly dividing cells (Frei, 1985). The aim of using both treatments is to kill off cancer cells that started and progressed because of genetic mutations.

The field of oncology had embraced cancer genetics, recognizing the molecular events involved in the carcinogenesis process and was, therefore, primed for the genomic era (see Figure 2).

In 1996, the National Cancer Institute (NCI) established the Office of Cancer Genomics (OCG) to make resources, technology, and databases available to improve the identification of normal functioning genes compared to those in tumors. The goal of OCG was to provide a technology and research infrastructure to help to identify groups of genes and how their interactions influenced cancer with the goal of “improving cancer prevention, early detection, diagnosis, and treatment of cancer” (NCI OCG, 2009). Then, the mapping of the human genome (Venter et al., 2001) catapulted oncology research and genetic technology to rapidly identify the genes and their related functions involved in the carcinogenesis process. As a result, OCG launched several research initiatives, including

• The Cancer Genome Anatomy Project (CGAP) (http://cgap.nci.nih.gov)—to identify in normal tissue which genes are active or normally turned off. Any given normal tissue (e.g., prostate tissue) has its own profile of working genes, a gene profile. Then gene changes in precancerous or cancerous tissue are identified compared to the normal tissue. All the information on normal, precancerous, or tumor profiles is stored in a database for research and clinical use (CGAP, 2008).
• The Initiative for Chemical Genetics (http://ocg.cancer.gov/programs/icg.asp)—to study the biology of cancer using small molecules (e.g., studying manmade molecules that can be used for new screening markers or targets for drug development). All the data about the small molecules are put in a data bank where they can be used for cancer research or biologic investigation (Tolliday et al., 2006).
• The Cancer Genome Atlas (http://ocg.cancer.gov/programs/tcga.asp)—to identify the normal gene activity (gene profile) and gene changes (tumor profile) in three specific cancers (brain, lung, and ovarian) to learn about the normal gene functions and what gene malfunctions affect carcinogenesis in these tissues. This research effort received a funding boost for 2010 with plans to collect more than 20,000 tissue samples from more than 20 cancer types, complete maps of the genomic changes in 10 of those cancers, and sequence and characterize at least 100 tumors of as many as 15 additional cancers. These maps will be deposited into public databases for use by the worldwide research community in research programs aimed at finding new ways to diagnose, treat, and prevent cancer.
• The Cancer Genetic Markers of Susceptibility (http://ocg.cancer.gov/programs/cgems.asp)—to scan more than 500,000 common genomic variations that may play a role in prostate and breast cancer.
• The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Initiative (http://ocg.cancer.gov/programs/target.asp)—to find the genomic changes associated with acute lymphocytic leukemia and neuroblastoma, two childhood cancers, in order to speed treatment discoveries for these cancers.

Based on these initiatives and other resulting research, staggering advances in genomic technology have emerged, which affect the detection of predisposition to cancer, diagnosis, and treatment. Two pivotal technology advances have been in DNA and proteomic microarray technology. Microarray is the use of chip technology. In DNA microarray, a chip about the size of a laboratory slide compares thousands of genes from normal and cancer tissue at the same time. The proteomic microarray examines the protein patterns activated most often in cell signals within cancer cells. Proteins in cancer cells also are examined with mass spectrometry. This microarray technology has strengthened discoveries in tumor profiles, finding gene markers for cancer screening, cancer recurrence potential or metastasis, and treatment targets. Now cancer tissue is examined not only by pathology, looking at the types of cells, but with molecular diagnosis looking at the genes and protein information from cancer tissue to aid in the diagnosis, staging, and treatment decisions in cancer (NCI, 2005).

Genetic and Genomic Advances Affect Oncology Nursing

Genetic and genomic technology advances affect all aspects of oncology care and therefore have direct implications for the role of the oncology nurse. Oncology nurses serve as translators and mediators of scientific and medical information given to clients to facilitate referrals, services, treatment, and follow-up care. More than ever, oncology nurses are challenged to be the knowledgeable interface between their clients and the information stemming from these genomic advances (Loescher & Merkle, 2005).

Understanding the genetic and genomic mechanisms of cancer etiology, diagnosis, and treatment is now central to the role of the oncology nurse. In response to this recognition, oncology nurses collaborated with the American Nurses Association (ANA) to spearhead the development of Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics for all RNs regardless of academic preparation, role, or clinical specialty (Jenkins & Calzone, 2007). The competencies were designed to delineate expectations of the entire nursing workforce when delivering genetically and genomically competent health care. Oncology Nursing Society, along with 48 other professional nursing organizations, endorsed the Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics (Consensus Panel on Genetic/Genomic Nursing Competencies, 2006). A second edition of the competencies, which included outcome indicators, was released in 2009 (Consensus Panel on Genetic/Genomic Nursing Competencies, 2009). An action plan is in progress for the integration of the competencies into curricula, licensure and registration examinations, specialty certification processes, and continuing nursing education. These competencies provide a framework upon which oncology nurses can build their specialty knowledge to be able to provide competent care both now and in the future.

New Discoveries, New Technology, New Content

Since the publication of Genetics in Oncology Nursing: Cancer Risk Assessment (Tranin et al., 2003), new genetic and genomic discoveries have influenced the fundamental understanding of cancer development, diagnosis, prognosis, and treatment. This, in turn, has created a demand for oncology nurses who are knowledgeable and competent in genetic and genomic applications affecting practice. The focus of Genetics and Genomics in Oncology NursingPractice has been broadened from risk assessment to encompass the key concepts of cancer biology, the resulting clinical applications, and the scope of oncology nursing practice. The changes include updated information in cancer genetic risk assessment and the addition of several new chapters reflecting the clinical use of genetics and genomics in oncology practice. The table of contents is organized into six sections to give the reader an overview of the principles, practice areas, clinical application, and issues related to genetics and genomics of cancer. The framework for every chapter follows the Essentials of Genetic and Genomic Nursing: Competencies, Curricula Guidelines, and Outcome Indicators (Consensus Panel on Genetic/Genomic Nursing Competencies, 2009). Each chapter begins with the competencies that are integral to the chapter content and practice issues. The sections and chapters are as follows.

Section I. Genetic and Genomic Fundamental Principles for Oncology Nursing

Chapter 1. “The Scope of Cancer Genetics and Genomics Nursing Practice” (Rewritten) provides nurses with information on how genetics and genomics influence the scope and standards and the dimensions of care at the basic and advanced levels of nursing practice.

Chapter 2. “Biology of Cancer” (Updated) focuses on the basic principles of genetics and the carcinogenesis process. New information in the chapter includes the role of epigenetics, oncogene classification, newly discovered mechanisms of tumor suppressor genes, and gene regulation in the cell cycle.

Section II. Cancer Genetic Risk Assessment, Education, and Management

Chapter 3. “How to Perform a Cancer Genetic Risk Assessment” (Updated) discusses the components of cancer risk assessment to identify high-risk individuals who may benefit from further genetic evaluation or risk-reduction interventions. New information is given on developing a differential list of cancer syndromes.

Chapter 4. “Common Risk Prediction Models and Cancer Risk Communication” (Updated) provides the reader with information about how to evaluate and when to use risk prediction models in cancer risk assessment. New content about ways to present risk information is provided.

Chapter 5. “Delivering Genetic Education and Counseling Services” (Updated) covers the elements of cancer risk education and counseling, delivery modes, and psychosocial considerations.

Chapter 6. “Establishment of a Cancer Genetic Risk Assessment Program” (Updated) gives the reader the main components of a cancer genetic risk assessment program and points to consider when deciding when and how to start a program. New information is given on financial and billing issues and considerations for selecting laboratories for genetic testing.

Chapter 7. “Genome-Wide Association Studies and Cancer” (New) explains the role of single nucleotide polymorphisms in disease development. Technology used in genome-wide association studies is described and details how common genetic variants related to genetic variation across the entire human genome are identified.

Section III. Impact of Genetic and Genomic Information on Cancer Care and Management

Chapter 8. “Tumor Profiling” (New) describes gene expression profiles, molecular diagnostics, and the techniques used in tumor profiling (i.e., DNA microarray assays). The chapter also describes clinical trials that use tumor profiles for the prediction of recurrence and evaluation of the effectiveness of treatment.

Chapter 9. “Pharmacogenomics” (New) provides the history of pharmacogenetics and pharmacogenomics, current discoveries, and implications for nursing practice with today’s oncologic treatments and regimens.

Chapter 10. “Targeted Therapies” (New) describes how genetic tumor profiles and other cellular factors, such as growth factors, influence tumor growth and make each cancer unique. The chapter discusses how the tumor’s unique profile and cellular environment are targets for cancer treatment.

Section IV. Ethical, Legal, and Social Issues of Genetics and Genomics

Chapter 11. “Handling Genetic and Genomic Information Responsibly” (Updated) explores emerging ethical issues in genetics and genomics and how nurses can apply existing ethical, social, and legal principles to these issues. Some of these issues include direct-to-consumer marketing and genetic testing, preimplantation genetic diagnosis and prenatal genetic testing for adult-onset genetic disorders, oversight of genetic testing, cancer predisposition genetic testing in children, stem cell research, and human cloning.

Chapter 12. “Multicultural Considerations in Providing Genetic and Genomic Cancer Care” (New) defines multicultural considerations in cancer nursing in the context of delivering genetic and genomic care to individuals, families, and communities. The chapter examines how genetics and genomics affect nurses’ understanding of culture, race, and ethnicity and the implications of genetic variations on the delivery of culturally competent nursing care.

Section V. Professional Practice Issues

Chapter 13. “Genetic/Genomic Competencies and Recommendations for Education” (Updated) defines what all nurses should know about genetics and genomics and how the Essentials of Genetic and Genomic Nursing: Competencies, Curricula Guidelines, and Outcome Indicators were developed and are now being implemented into nursing training and practice.

Chapter 14. “Ensuring Competence: Nursing Credentialing in Cancer Genetics” (New) discusses the significance of credentialing to nursing practice and the history of certification for oncology nurses and nurses in genetics. The chapter spells out the ways nursing has validated genetic and genomic nursing competence, provides information for nurses who specialize in oncology and genetic settings, and examines methods used to demonstrate their knowledge, skills, and abilities to provide care that meets professional standards of practice.

Chapter 15. “Research: Making a Difference in Practice” (New) explores the current research environment with a focus on how genetic and genomic oncology research will be translated into practice. Selected research initiatives, genetic nursing initiatives, and challenges for genetic nursing research for the future are presented.

Section VI. Resources

Chapter 16. “Identifying Appropriate Referrals and Resources” (Updated) describes resources important for professional networking, continuing education, client education, and clinical reviews. Listings of Web sites are provided to help nurses access the resources needed to stay current in genetics and genomics.

Genetic and Genomic Glossary. (Updated). An expanded glossary provides peer-reviewed definitions for related terms found bolded throughout the text.

Where We Are Going

As evident throughout this text, advances in the understanding of the genetic and genomic contributions throughout the cancer continuum are occurring at a rapid rate. The more that is learned, the more complex the cancer process appears to be. Discoveries from new programs of research are constantly arriving on the scene that can make a difference in the care that oncology nurses provide. What is described in this text is only the tip of the iceberg, with great hopes for the future of cancer care. This creates a tremendous responsibility for oncology nurses to be able to attain, synthesize, and then explain to clients and their families the emerging research results.

Clients, appropriately so, are most interested in knowing what this genetic and genomic information means to their health and well-being. Nurses have the opportunity to use such information to personalize cancer care. Many examples of tools and resources already are available to personalize cancer care (NCI, 2009). Nurses should pay attention in the years ahead to genetic and genomic research that builds on these advances that can make a difference in the care that they provide.

Genomic Variation: What Is It? How Is It Measured? What Difference Does It Make?

Personalized genetic variation screening tests can benefit patient response, guide the drug development process, and facilitate prescriber treatment selection. The potential for reducing drug-associated morbidities or even mortalities is tremendous because of the adverse events that could be avoided when using pharmacogenetic and pharmacogenomic information. The field of pharmacogenomics has made strides in identifying inherited genetic variations associated with medication metabolism and efficacy, with the goal of tailoring treatment to an individual’s genomic makeup (Weinshilboum & Wang, 2006). Newer approaches are combining multigene analysis of the individual’s genetic metabolic profile, tumor profile, and drug cellular pathways. For example, molecular diagnostic tools evaluate gene expression patterns in normal versus cancerous biospecimen samples and identify targets for treatment. Proteomics, the study of the structure and function of proteins and how they interact with each other, is an example of ongoing genomic variation research utilizing molecular characteristics to understand a patient’s predisposition for or experience with cancer. Researchers also are studying this combined genomic analysis to determine the relationship of chemotherapy toxicity with the genetic metabolic profile, drug targets, and efflux transporters (van Erp et al., 2009). Cells have efflux transporters to pump a drug in or out of the targeted cell to keep a nontoxic balance of a drug within the cells. However, some individuals have genetic variations causing increased drug transport out of the cell that decreases the drug effectiveness (Netterwald, 2009). These combined genomic evaluations are broadening pharmacogenomic approaches in oncology treatment. Understanding these genomic variations and their interaction will result in (a) the creation of new cancer screening tools, (b) the design of new targeted treatments, (c) mechanisms to determine and monitor treatment effectiveness, and (d) the ability to predict the patient’s response to treatment (NCI, 2005).

Health disparities in cancer outcomes is variation in cancer treatment and prevention outcomes because of genetic and genomic reasons or a combination of inherited risk, societal factors, environmental exposures, and personal behaviors. For example, molecular profiling of breast cancers according to their gene expression has identified subtypes (Kurian et al., 2009). This study reported that the risk for a second primary breast cancer was influenced by hormonal status, age, race, and ethnicity. To study the molecular basis of cancer, researchers need adequate representation of racially and genetically diverse sources. A focus on ensuring that research participation reflects the different populations is crucial to ensuring that results can be applied to all individuals.

Do the Genetic and Genomic Changes That Occur Throughout a Lifetime, Often in Response to Something in the Environment (e.g., Stress, Drug, Toxicant), Influence Cancer Care?

Toxicogenomics is a field of research concerned with the influence of toxicants on the gene and how these may be altered for a defined health condition (Oregon Health and Science University, n.d.). Technologic advances and sensitive screening processes are important to understanding the influence of all variables that affect cancer treatment and prevention outcomes. For example, McWhinney and McLeod (2009) reported that germ line and somatic DNA samples were comparable when assessing cancer pharmacogenomic variants. This finding indicates that the utilization of either sample type will provide needed information to individualize treatment decisions. Resources and processes that standardize and improve upon the collection and interpretation of such information are essential.

How Can the Identification of Genetic and Genomic Variation Be Used to Improve Cancer Treatment?

The use of molecular disease characteristics to diagnose an individual’s type of cancer can enable the selection of the best treatment for that individual (e.g., lymphoma stratification [Dave et al., 2006]). Ongoing research will provide additional results to guide targeted therapy options, such as Vectibix® (Amgen, Inc.) for those with colon cancer who are KRAS negative (Amgen, 2009), identify those who may best benefit from such interventions (e.g., prophylactic breast surgery [Garcia-Etienne et al., 2009]), and guide in the design of new treatment options, such as olaparib for BRCA mutation carriers (Fong et al., 2009). This area of research has tremendous implications for treatment morbidity and mortality.

What Resources and Tools Are Needed to Improve Access and Use of Genetic and Genomic Information in Cancer Care?

Technologic software advances, personal genome assistants, and collaborative working groups are examples of resources that are on the horizon to facilitate the clinical application of genetic and genomic research advances. Software applications that integrate genetic and genomic content into electronic health records have the potential to improve upon the collection, documentation, and use of personalized health information. However, improvements to standards and guidelines are recommended to improve the integration of genetics and genomics into clinical care (Scheuner et al., 2009).

Dr. Andras Pellionisz presented personal genome assistants (PRWeb, 2009) as a way to identify the toxic substances that an individual should avoid (e.g., specific foods) based on that individual’s personal genome. This personal genome handheld applicator is available for $5,000. Other inventions to improve decision making and access to services are under way.

The potential for emerging personal and clinical applications of genomic information necessitates improved oversight of quality, cost, access, and utility of genomic applications. One collaborative effort aimed at developing processes for enhancing translation of research discoveries into clinical care is the Genomic Applications in Practice and Prevention Network (GAPPNet) (Khoury et al., 2009). Stakeholder meetings will define the activities and programs to be created for GAPPNet. Its proposed goal is to accelerate the effective integration of genomic information into clinical care.

How Do Other New Technologies, Such as Nanotechnology, Influence Personalized Healthcare Options That Integrate Genetics and Genomics?

NCI is coordinating efforts to use new technologies, materials, and devices developed through nanotechnology research (http://nano.cancer.gov) to improve upon currently available cancer care options. Applications from additional scientific and epidemiologic fields of study need to be considered.

Does Ongoing Research Address the Ethical Issues and Biobehavioral Aspects of Cancer Care That Integrate Genetic and Genomic Information?

This is an area of research that benefits from interdisciplinary collaboration and research focus. One research example reported by Clancy (2009) provides a clinical perspective on the use of prenatal or preimplantation diagnosis for later-onset inherited cancer predisposition. Such complex issues require considerable informed discussion by all care providers to address such policy issues when explaining options to clients and their families.

Summary

Nurses can anticipate that the growing knowledge of cancer genetics and genomics will serve to further the mission of the Oncology Nursing Society (n.d.): “to promote excellence in oncology nursing and quality cancer care.” Oncology nurses have an opportunity to model for other nurses how to build upon this foundational scientific understanding of how the DNA structure, function, and interaction within ourselves (i.e., our body), outside ourselves (i.e., the environment and other external influences), and between ourselves (i.e., communities and populations) modifies health care. This book is only a beginning step of that lifelong, evolving journey of the learning necessary to become aware of, use, and maintain competency in the genomic era of oncology nursing.

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