Clinical Genetics

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Essential Competencies in Genetics and Genomics for All Nurses

Nearly 50 organizations, including the Association of Women’s Health, Obstetric and Neonatal Nurses and the National Association of Neonatal Nurses, have endorsed the Essential Nursing Competencies and Curriculum Guidelines for Genetics and Genomics. The guidelines were developed by an independent panel of nurse leaders from clinical, research, and academic settings and published by the American Nurses Association and the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (Jenkins & Calzone, 2007). According to the guidelines, all nurses need to have minimal competencies in genetics and genomics regardless of their academic preparation, practice setting, or specialty. Some of the competencies most relevant to nurses in the area of maternity and woman’s health include:

Expanded Roles for Maternity and Women’s Health Nurses

The Oncology Nursing Society (ONS) (www.ons.org) has taken an active role in providing oncology nurses with the education and resources they need to integrate genetics and genomics into all phases of care for individuals and families affected by chance. ONS offers online updates, regional classes, and position statements related to genetics and genomics (Hamilton, 2009).

Importance of Family History

Completion of the Human Genome Project and the resultant identification of the inherited causes for many diseases has created a renewed interest in family history (Clarke, 2009; De Sevo, 2009; Dolan et al., 2007; Dolan & Moore, 2007; Feero et al., 2008; Ginsburg & Willard, 2009; Hinton, 2008; Soloman, Jack, & Feero, 2008; Wattendorf & Hadley, 2005). Although it is easy to be impressed by the almost 1900 genetic tests currently available, family history will most likely continue to be the single most cost-effective piece of genetic information. Rich and colleagues (2004) described family history as the most important tool for diagnosis and risk assessment in health care genetics and a critical tool in the use of predictive testing in primary care. Solomon and colleagues argued that a complete three-generation family history that includes ethnicity information concerning both sides of family is the best genetic “test” applicable to preconception care. When nurses and other clinicians conduct a family history, they can gain not only valuable information about the structure of the family and diseases that affect various individuals in the family, but also a rich understanding of family relationships, social context, occupations, lifestyle, and health habits. In addition, the process of collecting this information often facilitates the development of a relationship between the client/family and the clinician. In 2004, the U.S. Department of Health and Human Services launched the Family History Initiative by designating Thanksgiving Day as National Family History Day. The U.S. Surgeon General encouraged families to use their family gatherings as a time to talk about and collect important family health history. A number of family history tools are available free of charge online. One of the most widely used is the My Family Health Portrait (https://familyhistory.hhs.gov). Another recently developed tool is the family health history tool, Does it run in the family? that was developed by the Genetic Alliance (www.doesitruninthefamily.org).

Gene Identification and Testing

Initial efforts to sequence and analyze the human genome have proven invaluable in the identification of genes involved in disease and in the development of genetic tests. Hundreds of genes involved in diseases such as breast cancer, colorectal cancer, Alzheimer’s disease, and CF have been identified. The number of commercially available genetic tests continues to increase and can be found on GeneTests, a publicly funded genetics information resource for clinicians (www.ncbi.nlm.nih.gov/sites/GeneTests/?db=GeneTests).

Genetic testing involves the analysis of human DNA, ribonucleic acid (RNA), chromosomes (threadlike packages of genes and other DNA in the nucleus of a cell), or proteins to detect abnormalities related to an inherited condition. Genetic tests can be used to examine directly the DNA and RNA that make up a gene (direct or molecular testing), look at markers that are coinherited with a gene that causes a genetic condition (linkage analysis), examine the protein products of genes (biochemical testing), or examine chromosomes (cytogenetic testing). Cytogenetic analysis of malignant tissue has become a mainstay of oncology.

Most of the genetic tests now offered in clinical practice are tests for single-gene disorders in clients with clinical symptoms or who have a family history of a genetic disease. Some of these genetic tests are prenatal tests or tests used to identify the genetic status of a pregnancy at risk for a genetic condition. Current prenatal testing options include maternal serum screening (a blood test used to see if a pregnant woman is at increased risk for carrying a fetus with a neural tube defect or chromosomal abnormalities such as Down syndrome, trisomy 18 and trisomy 13), fetal ultrasound or sonogram (an imaging technique using high-frequency sound waves to produce images of the fetus inside the uterus), and invasive procedures (chorionic villus sampling and amniocentesis) (see Chapter 26 for discussion of these tests). Other tests are carrier screening tests used to identify individuals who have a gene mutation for a genetic condition but do not show symptoms of the condition because it is an autosomal recessive condition (e.g., CF, sickle cell disease, and Tay-Sachs disease). Another type of genetic testing is predictive testing, which is used to clarify the genetic status of asymptomatic family members. The two types of predictive testing are presymptomatic and predispositional. Mutation analysis for HD, a neurodegenerative disorder, is an example of presymptomatic testing. If the gene mutation for HD is present, symptoms of HD are certain to appear if the individual lives long enough. Testing for a BRCA1 gene mutation to determine breast cancer susceptibility is an example of predispositional testing. Predispositional testing differs from presymptomatic testing in that a positive result (indicating that a BRCA1 mutation is present) does not indicate a 100% risk of developing the condition (breast cancer).

In addition to using genetic tests to test for single-gene disorders in clients with clinical symptoms or who have a family history of a genetic disease, genetic tests are being used for population-based screening. For example, newborn screening for phenylketonuria (PKU) and other inborn errors of metabolism (IEMs) has been going on in the United States and many other countries for decades (Guttmacher et al., 2010; Kenner et al., 2008). Initially, state-mandated newborn screening in the United States was concerned with only a few conditions. With the advent of tandem mass spectrometry, the number of conditions tested for during newborn screening grew rapidly. Currently, most states use blood spots collected from newborns to test for at least 30 different metabolic and genetic diseases. The four conditions most commonly tested for are PKU, congenital hypothyroidism, galactosemia, and sickle cell disease. A complete list of conditions tested for in each state is available on the National Newborn Screening and Genetics Resource website.

Another type of population-based screening is carrier screening for single-gene disorders such as CF, sickle cell disease, and Tay-Sachs disease either preconceptually or prenatally. In 2001, the American College of Obstetricians and Gynecologists and the American College of Medical Genetics (ACOG & ACMG) began recommending that clinicians offer carrier screening for CF to individuals with a family history of CF, reproductive partners of individuals who have CF, and couples in whom one or both partners are Caucasian and are planning a pregnancy or seeking prenatal care (ACOG & ACMG, 2001). One outcome of this broader CF carrier screening is that more and more individuals are being informed they have a CF mutation. Unfortunately, the correlation between genotype (an individual’s collection of genes) and phenotype (an individual’s observable traits) is poor for many of the more than 1400 CF mutations identified to date. That is, whereas some CF mutations are associated with significant health problems (poor growth, greasy stools, and chronic respiratory problems) others are not. Because of this, the significance of many CF mutations is uncertain. As a result, nurses and other health care professionals are increasingly being asked to communicate results with uncertain significance to individuals and families during the preconception and prenatal period (Dolan et al., 2007). In 2008, the NHGRI held a workshop to discuss lessons learned and new opportunities for population-based carrier screening (www.genome.gov/27026048). One of the main conclusions from this workshop was that a more coherent and systematic approach is needed for the introduction of new tests into population-based screening programs.

Pharmacogenomics

One of the most promising clinical applications of the Human Genome Project has been pharmacogenomic testing (the use of genetic information to guide a client’s drug therapy) (Ginsburg & Willard, 2009). Associations between genetic variation and drug effect have been observed for a number of commonly used drugs, including warfarin, an anticoagulant commonly used to reduce the risk of thromboembolic events in clients with a history of deep vein thrombosis, pulmonary embolism, myocardial infarction, or atrial fibrillation (Lanfear & McCleod, 2007; Meckley, Gudgeon, Anderson, Williams, & Veenstra, 2010). Warfarin is a drug with a narrow therapeutic index; it can result in serious bleeding with supratherapeutic doses and thromboembolic events with subtherapeutic doses). Because of this and the fact that there is a great deal of inter- and intraclient dose variation, warfarin is one of the most common causes of serious adverse drug reactions. Fortunately there is mounting evidence that genotype-guided warfarin dosing may not only help reduce the serious adverse drug reactions commonly associated with warfarin, but increase dosing accuracy, shorten the time to dose stabilization, and help identify individuals who may require more frequent monitoring. In August 2007, the U.S. Food and Drug Administration (FDA) approved updated labeling for warfarin. The updated labeling acknowledges that individuals with variations in their CYP2C9 and VKORC1 genes may require a lower initial dose of warfarin. However, there are not enough clinical data yet to recommend that this type of testing be mandatory.

Pharmacogenomic testing can also be used to target therapies. Trastuzumab (Herceptin), a monoclonal antibody that specifically targets HER2/neu overexpressing breast tumors, is an example of a drug for which an obligatory genetic test has been developed (Ginsburg & Willard, 2009). The purpose of this obligatory genetic test is to identify the subset of women with breast cancer who overexpress HER2/neu. Women who overexpress HER2/neu are most likely the only breast cancer clients who will benefit from taking trastuzumab (www.herceptin.com/index.jsp).

Gene Therapy

In the early 1990s, a great deal of optimism was felt about the possibility of using gene therapy to correct a long list of inherited diseases. Generally, gene therapy involves inserting a healthy copy of the defective gene into the somatic cells (any cell of the body except sperm and egg cells) of the affected individual. Although the early optimism about gene therapy was probably never fully justified, gene therapy has now moved from preclinical to clinical studies for many diseases ranging from hemophilia and other single gene disorders to complex disorders such as cancer, human immunodeficiency virus, and cardiovascular disorders (Gillet, Macadangdang, Fathke, Gottesman, & Kimchi-Sarfaty, 2009). Early hype, failures, and tragic events, such as the death of Jessie Gelsinger (an 18-year-old male with an X-linked genetic liver disease who was the first person publicly identified as having died in a gene therapy clinical trial) have now largely been replaced by stepwise progress in carefully developed, scientifically precise clinical trails (Gillet et al.; Kohn & Candotti, 2009). Major challenges to gene therapy include figuring out how to target the right gene to the right location in the right cells, expressing the transferred gene at the right time, and minimizing adverse reactions.

Ethical, Legal, and Social Implications

Before the beginning of the Human Genome Project, widespread concern about misuse of the information gained through genetics research resulted in 5% of the Human Genome Project budget being designated for the study of the ethical, legal, and social implications (ELSIs) of human genome research. Two large ELSI programs were created to identify, analyze, and address the ELSIs of human genome research at the same time that the basic science issues were being studied. During the past decade, issues of high priority for these programs have been privacy and fairness in the use and interpretation of genetic information; clinical integration of new genetics technologies; issues surrounding genetics research, such as possible discrimination and stigmatization; and education for professionals and the general public about genetics, genetics health care, and ELSI of human genome research. Both ELSI programs have excellent websites that include large amounts of educational information, as well as links to other informative sites (www.genome.gov/10001618; www.ornl.gov/sci/techresources/Human_Genome/elsi/elsi.shtml).

The major risk associated with genetic testing concerns what happens with the information gained through testing: it may result in increased anxiety and altered family relationships; it may be difficult to keep confidential; and it may result in discrimination and stigmatization. More important, there is still a large gap between the ability to test for a genetic condition and the ability to treat the same condition. In addition, informed consent is difficult to ensure when some of the outcomes, benefits, and risks of genetic testing remain unknown. Also many of the tests being used are as yet imperfect—few have a 100% detection rate. Individuals and families who receive false-positive results (the test results falsely indicate that a person or fetus is affected by a genetic condition) may terminate an unaffected pregnancy or undergo unwarranted extreme measures such as bilateral prophylactic mastectomy. Individuals and families who receive false-negative results (the test results indicate that a person or fetus is not affected by a genetic condition when in fact the person or fetus is affected) may fail to follow surveillance strategies designed to improve their health outcomes because they have been falsely reassured that they are not at increased risk for a specific condition.

Factors Influencing the Decision to Undergo Genetic Testing

The decision to undergo genetic testing is seldom autonomous and based solely on the needs and preferences of the individual being tested. Instead, it is often a decision based on feelings of responsibility and commitment to others (Van Riper, 2005; Van Riper & McKinnon, 2004). For example, a woman who is receiving treatment for breast cancer may undergo BRCA1/BRCA2 mutation testing not because she wants to find out if she carries a BRCA1 or BRCA2 mutation, but because her two unaffected sisters have asked her to be tested, and she feels a sense of responsibility and commitment to them. A female airline pilot with a family history of HD, who has no desire to find out if she has the gene mutation associated with HD, may undergo mutation analysis for HD because she feels she has an obligation to her family, her employer, and the people who fly with her.

Decisions about genetic testing are shaped, and in many instances constrained, by factors such as social norms, where care is received, and socioeconomic status. Most pregnant women in the United States now have at least one ultrasound examination, many undergo some type of multiple-marker screening, and a growing number undergo other types of prenatal testing. The range of prenatal testing options available to a pregnant woman and her family may vary significantly, based on where the woman receives prenatal care and her socioeconomic status. Certain types of prenatal testing may not be available in smaller communities and rural settings (e.g., chorionic villus sampling and fluorescent in situ hybridization [FISH] analysis). In addition, certain types of genetic testing may not be offered in conservative medical communities (e.g., preimplantation diagnosis). Some types of genetic testing are expensive and typically not covered by health insurance. Because of this, these tests may be available only to a relatively small number of individuals and families: those who can afford to pay for them.

Cultural and ethnic differences also have a significant effect on decisions about genetic testing. When prenatal diagnosis was first introduced, the principal constituency was a self-selected group of Caucasian, well-informed, middle- to upper-class women. Today the widespread use of genetic testing has introduced prenatal testing to new groups of women, women who had not previously considered genetics services. The fact that many of the women undergoing prenatal testing may not share mainstream U.S. views about the role of medicine and prenatal care, the meaning of disability, or how to respond to scientific risks and uncertainties further amplifies the complexity of ethical issues associated with prenatal testing.

The genetic testing experience raises fundamental questions about the mutual obligations of kin. Are individuals morally obligated to alert extended family members about inherited health risks? Conversely, do extended family members have a moral obligation to participate in research designed to determine genetic risk when unwanted information about them may be generated in the process? Another important question that must be considered is “Whose gene is it?” This question is likely to stimulate a great deal of debate, especially in the area of preimplantation genetic testing.

Genetic Transmission

Human development is a complicated process that depends on the systematic unraveling of instructions found in the genetic material of the egg and the sperm. Development from conception to birth of a normal, healthy baby occurs without incident in most cases; occasionally, however, some anomaly in the genetic code of the embryo creates a birth defect or disorder.

Genes and Chromosomes

The hereditary material carried in the nucleus of each of the somatic cells determines an individual’s characteristics. This material, called deoxyribonucleic acid (DNA), forms threadlike strands known as chromosomes. Each chromosome is composed of the many smaller segments of DNA referred to as genes. Genes, or combinations of genes, contain coded information that determines an individual’s unique characteristics. The code is found in the specific linear order of the molecules that combine to form the strands of DNA. Genes control both the types of proteins that are made and the rate at which they are produced. Genes never act in isolation; they always interact with other genes and the environment.

All normal human somatic cells contain 46 chromosomes arranged as 23 pairs of homologous (matched) chromosomes; one chromosome of each pair is inherited from each parent. There are 22 pairs of autosomes that control most traits in the body, and one pair of sex chromosomes. Whereas the Y chromosome is primarily concerned with sex determination, the X chromosome contains genes that are involved in much more than sex determination. The larger female chromosome is called the X; the smaller male chromosome is the Y. Generally the presence of a Y chromosome causes an embryo to develop as a male; in the absence of a Y chromosome, the individual develops as a female. Thus in a normal female, the homologous pair of sex chromosomes are XX, and in a normal male, the homologous pair are XY.

Homologous chromosomes (except the X and Y chromosomes in males) have the same number and arrangement of genes. In other words, if one chromosome has a gene for hair color, its partner chromosome also will have a gene for hair color, and these hair-color genes will have the same loci or be located in the same place on the two chromosomes. Although both genes code for hair color, they may not code for the same hair color. Genes at corresponding loci on homologous chromosomes that code for different forms or variations of the same trait are called alleles. An individual having two copies of the same allele for a given trait is said to be homozygous for that trait; with two different alleles, the person is heterozygous for the trait.

The term genotype typically is used to refer to the genetic makeup of an individual when discussing a specific gene pair, but at times genotype is used to refer to an individual’s entire genetic makeup or all the genes that the individual can pass on to future generations. Phenotype refers to the observable expression of an individual’s genotype, such as physical features, a biochemical or molecular trait, and even a psychologic trait. A trait or disorder is considered dominant if it is expressed or phenotypically apparent when only one copy of an allele associated with the trait is present. It is considered recessive if it is expressed only when two copies of the alleles associated with the trait are present.

As more is learned about genetics and genomics, the concepts of dominance and recessivity have become more complex, especially in X-linked disorders. For example, traits considered to be recessive may be expressed even when only one copy of a gene located on the X chromosome is present. This occurs frequently in males because males have only one X chromosome; thus they have only one copy of the gene located on the X chromosome. Whichever gene is present on the one X chromosome determines which trait is expressed. Females, conversely, have two X chromosomes, so they have two copies of the genes located on the X chromosome. However, in any female somatic cell, only one X chromosome is functioning (otherwise, there would be inequality in gene dosage between males and females). This process, known as X-inactivation or the Lyon hypothesis, is generally a random occurrence. That is, there is a fifty-fifty chance as to whether the maternal X or the paternal X is inactivated. Occasionally the percentage of cells that have the X with an abnormal or mutant gene is very high. This helps explain why hemophilia, an X-linked recessive disorder, can clinically manifest itself in a female known to be a heterozygous carrier (a female who has only one copy of the gene mutation). It also helps explain why traditional methods of carrier detection are less effective for X-linked recessive disorders; the possible range for enzyme activity values can vary greatly, depending on which X chromosome is inactivated.

Chromosomal Abnormalities

Chromosomal abnormalities are a major cause of reproductive loss, congenital problems, and gynecologic disorders; the incidence is approximately 0.6% in newborns, 6% in stillbirths, and 60% in spontaneous abortions (Martin, 2008). Errors resulting in chromosomal abnormalities can occur during mitosis (cell division occurring in somatic cells that results in two identical daughter cells containing a diploid number of chromosomes) or meiosis (division of a sex cell into two and four haploid cells). These errors can occur in either the autosomes or the sex chromosomes. Even without the presence of obvious structural malformations, small deviations in chromosomes can cause problems in fetal development.

The pictorial analysis of the number, form, and size of an individual’s chromosomes is known as a karyotype. Cells from any nucleated, replicating body tissue (not red blood cells, nerves, or muscles) can be used. The most commonly used tissues are white blood cells and fetal cells in amniotic fluid. The cells are grown in a culture and arrested when they are in metaphase (during metaphase, the chromosomes are condensed and visible with a light microscope), and then the cells are dropped onto a slide. This breaks the cell membranes and spreads the chromosomes, making them easier to visualize. Next the cells are stained with special stains (e.g., Giemsa stain) that create striping or “banding” patterns. These patterns aid in the analysis because they are consistent from person to person. Once the chromosome spreads are photographed or scanned by a computer, they are cut out and arranged in a specific numeric order according to their length and shape. The chromosomes are numbered from largest to smallest, 1 to 22, and the sex chromosomes are designated by the letter X or Y. Each chromosome is divided into two “arms” designated by p (short arm) and q (long arm). A female karyotype is designated as 46, XX and a male karyotype is designated as 46, XY. Figure 3-1 illustrates the chromosomes in a body cell.

Patterns of Genetic Transmission

Heritable characteristics are those that can be passed on to offspring. The patterns by which genetic material is transmitted to the next generation are affected by the number of genes involved in the expression of the trait. Many phenotypic characteristics result from two or more genes on different chromosomes acting together (referred to as multifactorial inheritance); others are controlled by a single gene (referred to as unifactorial inheritance). Specialists in genetics (e.g., geneticists, genetic counselors, and nurses with advanced expertise in genetics and genomics) predict the probability of the presence of an abnormal gene from the known occurrence of the trait in the individual’s family and the known patterns by which the trait is inherited.

Gene Mutations That Can Lead to Cancer

There are three main ways that people acquire gene mutations that can lead to cancer. The first is from the environment. Known factors in the environment that cause cancer are ultraviolet (UV) light (skin cancer) and tobacco smoke (lung cancer). The second way that people acquire mutations is by chance. Normal metabolic processes can generate chemicals that damage DNA. Third, people inherit mutations from their parents; hereditary mutations are thought to be a major factor in about 5% to 10% of all cancers.

The two main types of genes that have been recognized as playing a critical role in the development of cancer are oncogenes and tumor suppressor genes (American Cancer Society, 2010). Oncogenes are mutated forms of proto-oncogenes. The main functions of proto-oncogenes are to encourage and promote normal growth and development. When proto-oncogenes mutate to become carcinogenic oncogenes, the result is excessive cell multiplication. The activation of oncogenes has been compared to a jammed accelerator in a car. Most mutations of proto-oncogenes are acquired mutations, such as mutations in the KIT gene which are thought to cause most cases of gastrointestinal stromal tumor (GIST). This type of cancer can be treated with drugs that target the KIT gene, such as imatinib (Gleevec). Two examples of inherited mutations of proto-oncogenes are ERBB2, located on chromosome 13, and KRAS2, located on chromosome 12. ERBB2 is involved in breast, ovarian, lung, gastric, and salivary gland cancers. KRAS2 is involved in breast, pancreatic, thyroid, colorectal, bladder, and lung cancers, as well as acute myeloid leukemia.

Tumor suppressor genes normally function to inhibit or “put the brakes on” the cell growth and division cycle. They function to prevent the development of tumors. Mutations in tumor suppressor genes cause the cell to ignore one or more of the components of the network of inhibitory signals, removing the brakes from the cell cycle. This results in a higher rate of uncontrolled growth: cancer. Acquired mutations of the TP53 gene appear in a wide range of cancers, including lung, colorectal, and breast cancer. Examples of inherited tumor suppressor genes include APC, located on chromosome 5 and involved with familial adenomatous polyposis of the colon (FAP); BRCA1, located on chromosome 17 and associated with hereditary breast cancer and ovarian cancer; and RB1, found on chromosome 13 and involved with familial retinoblastoma.

Hereditary Breast and Ovarian Cancer

Breast cancer is a common disease and a central concern in women’s health. In the United States, breast cancer is the most common form of cancer for women and the second most common cause of death. Hereditary mutations are considered to be a key factor in approximately 5% to 10% of all breast and ovarian cancers. Another 15% to 20% of female breast cancers occur in women who have a family history of breast and ovarian cancer but do not carry a mutation in one of the genes that are known to be strongly associated with breast and ovarian cancer susceptibility.

BRCA1 and BRCA2 mutations account for approximately 70% to 85% of hereditary breast and ovarian cancer (HBOC). These mutations are inherited in an autosomal dominant pattern; thus each offspring of an individual found to carry a BRCA mutation has a 50% chance of inheriting the same mutation. Ashkenazi Jews are 10 times more likely to have BRCA1 and/or BRCA2 mutations than are the general population. According to estimates of lifetime risk, approximately 12% of women in the general population will develop breast cancer sometime during their lifetime, compared to about 60% of women who have inherited a deleterious mutation in their BRAC1 or BRCA2 gene (National Cancer Institute, 2010). Another way of saying this is that a woman with a deleterious BRCA1 or BRCA2 mutation is about five times more likely to develop breast cancer than a woman who does not carry a deleterious BRCA1 or BRCA2 mutation. Even though only about 6% of the men who carry a BRCA mutation develop breast cancer, men who carry a BRCA mutation have a 50% chance of passing the mutation on to their offspring. As far as lifetime risk estimates for ovarian cancer, about 1.4% of women in the general population will be diagnosed with ovarian cancer during their lifetime, compared with 15% to 40% of women who have a deleterious BRCA 1 or BRCA2 mutation. Carriers of BRCA1 mutations may also be at increased risk for colon cancer, though this has been disputed. Carriers of BRCA2 mutations may be at increased risk for pancreatic, prostate, gallbladder and bile duct, and stomach cancers, hematologic malignancies, and malignant melanoma.

Genetic testing for HBOC has been commercially available in the United States since 1995. The cost for testing (current in 2010) is approximately $3,000 for full-sequence BRCA1 and BRCA2 testing, and $350 for an analysis of relatives of an individual with an identified mutation. Women newly diagnosed with breast cancer are increasingly being asked to consider undergoing BRCA1 and BRCA2 testing before they make decisions about their treatment options. This request for testing is occurring because a number of studies have shown that a woman’s short-term risk of developing a second breast cancer is substantially affected by whether she carries a BRCA1 or BRCA2 mutation, and prophylactic surgery has been found to decrease the risk of breast and ovarian cancer by more than 90% (Hartmann, Degnim, & Schaid, 2004; McDonnell, Schaid, Myers, Grant, Donohue, Woods, et al., 2001; Rebbeck, Friebel, Lynch, Neuhausen, van’t Veer, Garber, et al., 2004). The main advantage to offering BRCA1 and BRCA2 testing before the onset of treatment is that it gives women who are found to carry a deleterious mutation the option of choosing risk-reduction surgery concurrent with therapeutic surgical treatment.

Colon Cancer

Colon cancer is the third leading cause of cancer-related death in women. According to estimates from the American Cancer Society (2010), 102,900 new cases of colon cancer and 39,670 new cases of rectal cancer were diagnosed in 2009 and there were 51,370 deaths due to colorectal cancer. Only 10% of colon cancer cases are likely to involve a mutation in one of several predisposing genes. Two examples of predisposing genes are mutations in the APC tumor suppressor gene and mutations in a mismatch repair gene. Mutations in the APC tumor suppressor gene have been associated with FAP, a rare, autosomal dominant syndrome that accounts for about 1% of all colon cancer. It is typically diagnosed clinically. Affected individuals have 100 to 1000 polyps in their colon by the time they are 20 to 30 years old. Genetic testing is greater than 80% sensitive. Identification of high risk individuals guides surveillance strategies and the timing of a prophylactic colectomy. Low risk individuals can stop the increased surveillance.

Hereditary nonpolyposis colon cancer (HNPCC) results from mutations in one of many mismatch repair (MMR) genes. Mutations in MSH2 and MLH1 account for 50% to 60% of HNPCC. Families at high risk for HNPCC often have three or more relatives with colorectal cancer; colorectal cancer present in at least two generations; and a diagnosis of colorectal cancer before age 50 years in at least one case. HNPCC is characterized by an increased risk of colon cancer and other cancers that include cancers of the ovary, endometrium, stomach, small intestine, upper urinary tract, hepatobiliary tract, brain, and skin. The lifetime risk of colon cancer for individuals with HNPCC is approximately 80%. The majority of these cancers occur in the proximal colon. Genetic tests are available to test for MSH2 and MLH1. Testing should be done first on the affected family member. At-risk clients should be offered a prophylactic colectomy. Women may be offered a total abdominal hysterectomy with a salpingo-oophorectomy to decrease cancer risk. If colon cancer develops, a total colectomy is recommended.

Definition of Genetic Counseling

In 1975 an ad hoc committee of the American Society of Human Genetics developed a formal definition of genetic counseling. According to this definition:

Genetic counseling is a communication process that deals with the human problems associated with the occurrence or risk of occurrence of a genetic disorder in a family. This process involves an attempt by one or more appropriately trained person to help the individual or family to (1) comprehend the medical facts including the diagnosis, probable course of the disorder, and the available management; (2) appreciate the way heredity contributes to the disorder and the risk of recurrence in specified relatives; (3) understand the alternatives for dealing with the risk of recurrence; (4) choose a course of action that seems to them appropriate in view of their risk, their family goals, and their ethical and religious standards and act in accordance with that decision; and (5) make the best possible adjustment to the disorder in an affected family member and/or to the risk of recurrence of that disorder.

Access and Referral to Genetic Counseling

Genetic counseling is typically provided by a team of genetics specialists that includes clinical geneticists (physicians with an MD or DO), medical geneticists with a PhD, genetics fellows, genetics counselors, and, in a growing number of cases, advanced practice genetics nurse specialists. Cytogeneticists, biochemical geneticists, and molecular geneticists support the clinical genetics team by providing laboratory expertise that helps with the diagnosis and management of individuals and families affected by genetic conditions.

Until recently, most individuals and families interested in receiving genetic counseling went to regional genetics centers or major medical centers. Genetic counseling also was provided in outreach or satellite genetics clinics, public health clinics, and some community hospitals. Now that genetics is entering the mainstream of health care, genetic counseling is being offered in a wide variety of other settings. These include, but are not limited to, managed health care organizations, commercial facilities, and private practices. A number of specialized groups provide genetics education and counseling for individuals and families affected by specific genetic disorders, such as DS, CF, diabetes, muscular dystrophy, HD, and cancer. Genetic counseling also is offered over the Internet.

Individuals and families seek out, or are referred for, genetic counseling for a wide variety of reasons and at all stages of their lives. Some seek preconception or prenatal information; others are referred after the birth of a child with a birth defect or a suspected genetic condition; still others seek information because they have a family history of a genetic condition. Regardless of the setting or the individual and family’s stage of life, genetic counseling should be offered and available to all individuals and families who have questions about genetics and their health. However, there is currently a shortage of appropriately trained genetics professionals who can provide genetic counseling. This means that many individuals and families will not be offered genetic counseling when they undergo genetic testing. Moreover, some of the genetics education and counseling that is provided will be inadequate.

It may take years before a sufficient number of health care professionals feel comfortable and are proficient in providing genetic counseling (Burke & Kirk, 2006; Cashion, 2009). Until then it is imperative that all health care professionals become familiar with existing genetics resources, such as the Centers for Disease Control and Prevention, the Genetic Alliance, the National Coalition for Health Professional Education in Genetics, Genetics Education Program for Nurses at Cincinnati Children’s Hospital Medical Center, NHGRI Education, and others. Some of these resources may be in health care professionals’ own communities, but others are regional, national, and international.

Estimation of Risk

Most families with a history of genetic disease want an answer to the following question: What is the chance that our future children will have this disease? Because the answer to this question may have profound implications for individual family members and the family as a whole, health care professionals must be able to answer this question as accurately as they can in a timely manner. In some cases, estimation of risk is rather straightforward; in other cases, it is complicated. Because of this, health care professionals should be prepared to refer families with a history of genetic disease to genetics professionals if they are at all unsure. Again, the answer to this question can have profound implications for individual family members and the family as a whole, so health care professionals must do their best to ensure that the question is answered accurately.

If a couple has not yet had children, but they are known to be at risk for having children with a genetic disease, they will be given an occurrence risk. Once the mating of a couple has produced one or more children with a genetic disease, the couple will be given a recurrence risk. Both occurrence and recurrence risks are determined by the mode of inheritance for the genetic disease in question. For genetic diseases caused by a factor that segregates during cell division (genes and chromosomes), risk can be estimated with a high degree of accuracy by application of mendelian principles.

In an autosomal dominant disorder, both the occurrence and recurrence risk is 50%, or one in two, when one parent is affected and the other is not. The recurrence risk for autosomal recessive disorders is 25%, or one in four, if both parents are carriers (they each have one recessive disease gene and one normal gene). Occasionally an individual homozygous for a recessive disease gene mates with an individual who is a carrier of the same recessive gene. In this case, the recurrence risk is 50%, or one in two. If two individuals affected by an autosomal recessive disorder mate, all of their children will be affected (See Fig. 3-3). For X-linked disorders, recurrence risk is related to the sex of the child. Translocation disorders have a high risk of recurrence.

A number of autosomal disorders display fairly complex patterns of inheritance, making estimation of risk somewhat difficult. For example, if a child is born with a genetic disease and there has been no history of the disease in the family, the disease may have been caused by a new mutation (this is more likely if the disease in question is an autosomal dominant disorder, such as achondroplasia). If the child’s genetic disease has been caused by a new mutation, the recurrence risk for the parents’ subsequent children is low (1% to 2%), but it is not as low as that for the general population. Offspring of the affected child may have a substantially elevated occurrence risk.

The risk of recurrence for multifactorial conditions can be estimated empirically. An empiric risk is based not on genetics theory but rather on experience and observation of the disorder in other families. Recurrence risks are determined by applying the frequency of a similar disorder in other families to the case under consideration.

An important concept to be emphasized to individuals and families during a genetic counseling session is that each pregnancy is an independent event. For example, in monogenic disorders in which the risk factor is one in four that the child will be affected, the risk remains the same no matter how many affected children are already in the family. Families may maintain the erroneous assumption that the presence of one affected child ensures that the next three will be free of the disorder. However, “chance has no memory.” The risk is one in four for each pregnancy. Conversely, in a family with a child who has a disorder with multifactorial causes, the risk increases with each subsequent child born with the disorder.

Interpretation of Risk

The guiding principle for genetics counselors has traditionally been nondirectiveness. According to the principle of nondirectiveness, the individual who is providing genetic counseling respects the right of the individual or family being counseled to make autonomous decisions. Counselors using a nondirective approach avoid making recommendations and try to communicate genetics information in an unbiased manner. The first step in providing nondirective counseling is becoming aware of one’s own values and beliefs. Another important step is recognizing how those values and beliefs can influence or interfere with the communication of genetics information.

If the individual who is providing genetic counseling has difficulty being nonjudgmental and objective, he or she may either intentionally or unintentionally influence the decision-making process. Individuals and families also may pressure the counselor to make decisions for them with questions such as, “What would you do if you were me?” Families and individuals need education, guidance, and support throughout the counseling process. They should be given the facts and possible consequences, as well as all of the assistance they need in problem solving, but the final decision regarding a course of action must be their own.

Multiple Roles for Nurses in Genetics

Nurses play many roles in genetics. Some nurses play a key role in the identification of families in need of genetic counseling, and they collaborate with other health care professionals to make referrals to specialists in genetics. Other nurses take a more active role in genetic counseling. For example, these nurses might provide appropriate genetics information before, during, and after the initial genetic counseling session; construct family pedigrees of three or more generations; clarify the genetics information that family members receive during counseling sessions or from other sources such as the public library, the Internet, or support groups; help families manage the ongoing challenges associated with living with a genetic disorder; make referrals to support groups and national organizations; and provide long-term follow-up of families affected by genetic conditions.

Probably the most important of all nursing functions is to provide emotional support during all aspects of the counseling process. Feelings that are generated under the real or imagined threat posed by a genetic disorder are as varied as the people being counseled. Responses may include a variety of stress reactions, such as apathy, denial, anger, hostility, fear, embarrassment, grief, and loss of self-esteem. Guilt and self-blame are universal reactions. Many look on the disorder as a stigma, especially if the disorder is visible to others. Old wives’ tales, superstitions, and long-held misconceptions may influence a family’s reaction to a genetic disorder (Clinical Reasoning).

• Recent advances in molecular biology and genomics have revolutionized the field of health care by providing the tools needed to determine the hereditary component of many diseases.

• Increasingly, nurses from all specialty areas, as well as all practice settings, are expected to have competencies in genetics and genomics.

• The major force behind the genetics revolution has been the Human Genome Project.

• All humans are 99.9% identical at the DNA level.

• Approximately 20,000 to 25,000 genes are found in the human genome.

• Most of the genetic tests being offered in clinical practice are tests for single-gene disorders.

• Pharmacogenomics will probably be the most immediate clinical application of the Human Genome Project.

• The decision to undergo genetic testing is often based on feelings of responsibility and commitment to others.

• Genes are the basic units of heredity responsible for all human characteristics. They comprise 23 pairs of chromosomes: 22 pairs of autosomes and 1 pair of sex chromosomes.

• Chromosomal abnormalities occur in autosomes and sex chromosomes.

• Multifactorial inheritance includes genetic and environmental contributions.

• Advances in genetics have complex ethical, legal, and social implications.

• Cancer genetics is an important emerging field.