Implications of Genetics and Genomics for Nurses

1. Implications of Genetics and Genomics for Nurses Dale Halsey Lea, MPH, RN, CGC, FAAN Consultant, Public Health Genomics And Ellie Mulcahy, RNC MaineCDC Genetics Program

2. Learning Objectives • Describe the core competencies for nurses in genetics and genomics. • Describe personalized medicine and what this means for nursing practice. • Give two examples of the role of pharmacogenomics in treating diseases.

3. Yesterday’s Genetics • Chromosomes – units of heredity inside cells – first discovered in the late 1800’s. • Early 1900’s – inherited diseases first linked to chromosomes. • 1950’s – 1980’s – genetic tests for genetic conditions affecting children such as cystic fibrosis, Down syndrome and Duchenne muscular dystrophy were developed.

4. Yesterday’s Genetics • Genetic testing used to make or confirm a diagnosis, and to screen newborns for conditions such as PKU so early interventions and treatments could be administered. • Very few research laboratories capable of conducting genetic testing, and few commercial genetic testing laboratories.

5. Today’s Genetics and Genomics • NHGRI lead the Human Genome Project for the National Institutes of Health. • The full human genome sequence was completed in April 2003. • NHGRI now moves forward into the genomic era with research aimed at improving health and fighting disease.

6. Personalized Medicine • Pre-genome era: healthcare providers used a “one size fits all” approach to treating individuals. • Post-genome era: increasingly healthcare providers will be able to use genomic information to tailor treatments to the individual, and personalize their care.

7. Genomic Healthcare: What it Means for Nurses • Increasing use of genetic and genomic technologies to screen, diagnose and treat rare and common diseases. • Nurses must be knowledgeable and competent in providing genetic and genomic-based healthcare.

8. Essential Nursing Competencies in Genetics and Genomics Demonstrate an understanding of the relationship of genetics and genomics to health, prevention, screening, diagnostics, prognostics, selection of treatment, and monitoring of treatment effectiveness. Use genetic-and genomic-based interventions and information to improve clients’ outcomes.

9. Essential Nursing Competencies in Genetics and Genomics Perform interventions/treatments appropriate to clients’ genetic and genomic healthcare needs. Evaluate impact and effectiveness of genetic and genomic technology, information, interventions, and treatments on client outcomes. (Reference: American Nurses Association (2009). Essentials of Genetic and Genomic Nursing: Competencies, Curricula Guidelines, and Outcome Indicators. 2nd Edition, Silver Spring, MD)

10. Genetics and Genomics Defined Genetics – the study of individual genes and their impact on relatively rare, single gene disorders. Genomics – the study of all genes in the human genome together, including their interactions with each other, the environment, and the influence of other psychosocial and cultural factors.

11. Genotype and Phenotype • Genotype – an individual’s collection of genes • The expression of a person’s genotype contributes to the individual’s observable traits. • Phenotype – the physical manifestation of a genotype in the form of a trait (height, eye color) or disease (cancer).

12. Case Example • Mrs. N is a 55 year old Caucasian female with a history of early onset breast cancer. She has had genetic testing to learn of the cause of her breast cancer and learns that she has a gene mutation in the BRCA1 gene. Several years later her daughter develops ovarian cancer. She also has genetic testing and is found to have the same BRCA1 mutation as her mother. She asks you, her oncology nurse, why if she has the same gene mutation as her mother she has ovarian cancer and not breast cancer. In keeping with the Genetic and Genomic Nursing Essential Competencies that nurses provide clients with interpretation of selective genetic and genomic information, you explain that the BRCA1 mutation is the genotype that she shares with her mother. However, how she is expressing the gene – called the phenotype – is not the same as her mother’s expression of the gene.

13. Hereditary vs. Somatic • Hereditary – Disorders that are transmitted through genes that have been passed from parents to their offspring (children). • Somatic – Disorders caused by alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases.

14. Penetrance Defined • The proportion of individuals with a mutation causing a particular disorder who exhibit clinical symptoms of that disorder. • Complete penetrance - A condition (most commonly inherited in an autosomal dominant manner) is said to have complete penetrance if clinical symptoms are present in all individuals who have the disease-causing mutation. • Reduced or incomplete penetrance – if clinical symptoms are not always present in individuals who have the disease-causing mutation.

15. Incomplete Penetrance – Case Example • Frank is a 59 year old Caucasian male with a history of Hereditary Hemochromatosis.  He has been found to have C282Y/H63D mutations as the cause of his hemochromatosis.  In going over his family history he tells you that neither of his parents had a history of hemochromatosis and although one of his brothers has cirrhosis of  the liver, two other brothers are healthy.  You explain that some people who carry a gene mutation may not show clinical symptoms of the disorder and this is called incomplete penetrance. 

16. Implications for Nurses • Examples of Nursing Roles in Genomic Health care: • Guide interventions for the prevention of cardiovascular disease in young adults. • Facilitate drug selection or dosage in treatment of an adult with cancer based on molecular markers. • Promote informed consent that includes the risks, benefits, and limitations of participation in genomic research. • Assist anyone having questions about genetic and genomic information or services, including genetic evaluation and counseling services. http://www.genome.gov/17517037

17. Genetic Testing • Pharmacogenetic genetic testing – • examines a person's genes to look at how drugs would move through the body and be broken down. • The goal of pharmacogenetic testing is to have drug treatments that are specific to each person.

18. Genetic Testing • Pharmacogenomic genetic testing – • examines the inherited variations in genes that dictate drug response, and • explores the ways these variations can be used to predict whether a patient will have a good response to a drug, a bad response to a drug, or no response at all.

19. Genetic Testing Is there a difference between pharmacogenomics and pharmacogenetics? • Pharmacogenomics refers to the general study of all of the many different genes that determine drug behavior. • Pharmacogenetics refers to the study of inherited differences (variation) in drug metabolism and response. • The distinction between the two terms is considered arbitrary, however, and now the two terms are used interchangeably.

20. Personalized Medicine • Personalized medicine has the potential to transform healthcare through: • earlier diagnoses, • more effective prevention and treatment of disease, • avoidance of drug side effects.

21. Clinical Pharmacogenetics in Pediatric Patients • Childhood Leukemia – Drug Response and Toxicity • The U.S. Food and Drug Administration (FDA) recommends genetic testing before giving the chemotherapy drug mercaptopurine (Purinethol) to patients with acute lymphoblastic leukemia, including children. • Some people have a genetic variant that interferes with their ability to process the drug. • This processing problem can cause severe side effects and increase risk of infection, unless the standard dose is adjusted according to the patient's genetic makeup

22. Clinical Pharmacogenetics in Pediatric Patients • Asthma – most common chronic disorder in children and adolescents, and leading cause of hospitalizations in children. • Albuterol (an inhaled B2 agonist) commonly used treatment. • Studies are now underway looking at how an asthma patient’s genotype affects response to Albuterol, and how doses can be modified based on genotype.

23. Clinical Pharmacogenetics in Adult Patients • In 2007, the FDA revised the label on the common blood-thinning drug warfarin (Coumadin) to explain that a person's genetic makeup might influence response to the drug. • Some doctors have begun using genetic information to adjust warfarin dosage. • Genetic testing can determine whether an adult patient is a poor metabolizer, intermediate or ultra-rapid metabolizer, and the dose of warfarin can be adjusted based on their specific metabolism. Still, more research is needed to conclusively determine whether warfarin dosing that includes genetic information is better than the current trial-and-error approach.

24. Clinical Pharmacogenetics in Patients Infected with HIV • One current use of pharmacogenomics involves people infected with the human immunodeficiency virus (HIV). • Before prescribing the antiviral drug abacavir (Ziagen), doctors now routinely test HIV-infected patients for a genetic variant that makes them more likely to have an adverse reaction to the drug.

25. Clinical Pharmacogenetics in Adult Patients • The FDA advises doctors to test colon cancer patients for certain genetic variants before administering irinotecan (Camptosar), which is part of a combination chemotherapy regimen. • Patients with one particular variant may not be able to clear the drug from their bodies as quickly as others. • This results in severe diarrhea and increased infection risk. • Such patients may need to receive lower doses of the drug.

26. Genetic Testing • Direct-to-consumer genetic testing – a new approach that allows people to order certain genetic tests by sending in a sample of their saliva or tissue to a laboratory. • The laboratory returns results only to the individual who sent in the sample. • Often no healthcare provider is involved in the process.

27. Genetic Testing • Direct-to-consumer genetic testing – should children have their genomes scanned? • Proactive family project – earlier opportunities for intervention and prevention? • Informed consent? • The DNA Innate Talent Test – testing children to identify genetic traits for intelligence, emotional quotient (EQ), athletic ability?

28. Genetics and Genomics Tomorrow • In the future: • Genetic testing will be used to scan all of a person’s genetic material, so that disease risk variants can be identified and early intervention and treatment can be planned. • The cost of testing an individual’s entire genome will be less than $1,000. • We will live in a time of “personalized medicine,” when many treatments for medical conditions will be chosen based upon what genetic testing indicates about a person’s specific genetic makeup.

29. Teaching Patients and Families About Genetic Testing: Nursing Roles • The registered nurse: • Provides clients with interpretation of selective genetic and genomic information or services. • Provides clients with credible, accurate, appropriate, and current genetic and genomic information, resources, services, and/or technologies that facilitate decision-making. • Uses genetic- and genomic-based interventions and information to improve clients’ outcomes. • Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics, 2009

30. Teaching Patients and Families About Genetic Testing: Nursing Roles • Explain: • What genetic testing is – genetic testing uses laboratory methods to look at your genes. • What the specific genetic test is that is being recommended/offered. • What will be learned about the client’s health from the genetic testing (e.g. diagnosis, to guide treatment). • How the genetic testing will be done. • Describe safeguards that will protect the privacy of the client’s test results.

31. Teaching Patients and Families About Genetic Testing: Nursing Roles • Provide resources to the client about where they can learn more about genetic testing: • National Human Genome Research Institute – www.genome.gov/health • Genetics Home Reference – http://ghr.nlm.gov/medlineplus/genetictesting.html • National Cancer Institute – www.cancer.gov/cancertopics/UnderstandingCancer/genetesting

32. Implications for Nurses • Nurses will be on the frontline in communicating genetic and genomic information to patients, families and communities. • All nurses need to be fluent in the language of genetics and genomics so they can provide effective nursing care. • The Essential Nursing Competencies in Genetics and Genomics provide a framework for nurses to practice genomic health care. • http://www.genome.gov/17517037