Did you know that you have the BRCA1 and BRCA2 genes? They are actually tumor suppressor genes present in both men and women. Normal tumor suppressor genes help prevent cancer. A loss-of-function defect or mutation within these genes can result in the accumulation of damaged DNA in certain cells. A loss of function or mutation in the BRCA1 and BRCA2 genes is associated with an increased risk for breast and ovarian cancer in women. BRCA1 mutations are more often associated with breast and ovarian cancer clusters in families, and BRCA2 mutations are more often associated with male breast cancer.¹

Genetic mutations can be responsible for a host of other illnesses, as well. One example is a hypercoagulation disorder involving the human Factor V gene. The human Factor V gene is associated with the production of the coagulation protein Factor V, a cofactor in the activation of thrombus. Factor V Leiden (FVL) is the name given to a mutation in Factor V that causes a hypercoagulation disorder called Factor V Leiden thrombophilia. It is the most common inherited form of thrombophilia.

Factor V is normally inactivated by another protein, activated protein C (aPC), to prevent excess clotting. However, the FVL mutation leads to a variant of Factor V that cannot be inactivated by aPC and can result in deep vein thrombosis (DVT) and other clotting problems.²

Many advances in medicine and health care have resulted from the Human Genome Project, www.genome.gov an international effort to sequence and map all the genes in the human complement of 46 chromosomes. (The genome is the full set of chromosomes carried within a human being). Completed in 2003, the Human Genome Project gave scientists the ability to read nature’s complete genetic blueprint for the creation of a human being. The Human Genome Project has provided an abundance of new knowledge about the association of genetics (the study of single genes and their role in inheritance) and genomics (the study of all of a person’s genes and their interactions with the environment) with human disease.³

While the functions for many of human genes are still being elucidated, these new developments mean that nurses must develop a foundation of knowledge about genetics and genomics on which they can base their nursing care and practice. With new genetic technologies and information, nurses must have the knowledge necessary to answer patients’ questions. Nurses have an advantage in caring for people seeking genetic information: They are usually the first healthcare professionals with whom patients speak and the first to perform visual and physical patient assessments and health histories.

The environment in which many nurses practice requires specific genetic knowledge crucial to the delivery of effective patient care.⁴ Nurses need to understand the relationship between genes and genetics and health and illness — and its impact on primary care nursing. Although currently not as developed as the science of genetics, the science of genomics will become more important in nursing in the future.⁵

Although some nurses may be worried about a steep learning curve,⁶ understanding how genetics and genomics fit into nursing practice is becoming less daunting with the many resources available today. One important resource is the Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics, www.genome.gov/17517146 established by nurse leaders from clinical, academic, government, and research settings.⁷ This continuing education module focuses on the activities in the guidelines that fall into the “professional practice” domain: assessment (applying and integrating genetic and genomic knowledge), identification (identifying clients who may benefit from genetic services), referral activities, and provision of education, care, and support.⁷

Nurses at every level and setting practice should be prepared to teach their patients about the implications of genetics and genomics for  common diseases, such as heart disease, diabetes, cancer, neurological disease, and mental illness.⁴ Nurses should learn and implement the activities of assessment, identification, referral, and the provision of education, care, and support, including genetic/genomic knowledge, for all patients.

This module will use information related to breast cancer and FVL, as well as the associated environmental and lifestyle choices that may influence these disorders, as examples to help nurses consider how to include genetic competencies and patient education in their practice.

BRCA genes

Consider the professional practice activities as they relate to breast cancer, ovarian cancer, and BRCA genes.

Assessment: A family history may reveal a disease trend for patients and their families and the need for additional follow-up by the practitioner. It may reveal that a patient’s sister had breast cancer and a paternal aunt died at age 48 of ovarian cancer. This may indicate that the patient is at risk for hereditary breast and ovarian cancer syndrome because of an inherited mutation in a BRCA gene, which can be passed from either parent to a male or female offspring. Inherited (germline) mutations are passed through the egg or sperm cells. 

Children of parents who have a BRCA1 or BRCA2 mutation have a 50% chance of inheriting the mutation (autosomal dominant inheritance).¹ In contrast, sporadic cancers result from mutations that occur during a person’s lifetime and are not passed from parent to offspring. Only 5% to 10% of all breast and ovarian cancers are hereditary, and increase the lifetime risk of American women from about a 12% chance of developing breast cancer and about a 2% chance of developing ovarian cancer. The BRCA1 and BRCA2 mutations affect about one in 800 people and increase the risk of developing breast, ovarian, and other cancers at a very early age.¹ 

Identification: A family history tool (available at the My Family Health Portrait website) https://familyhistory.hhs.gov can help in constructing a pedigree (family tree) using standardized symbols and terminology. A pedigree drawing allows practitioners to recognize a pattern of inherited cancer (or other disorders) in a patient’s family. 

The GeneTests website www.genetests.org has information on breast cancer screening services and government-regulated labs. The National Human Genome Research Institute www.genome.gov provides information to help practitioners understand genetic concepts and skills, find teaching cases, and understand the ethical, legal, social, and cultural issues related to genetic and genomic services.

A genetic dictionary

The National Cancer Institute explains many important terms in its Dictionary of Genetic Terms. www.cancer.gov/cancertopics/genetics-terms-alpha list/a-e One such term is “penetrance,” or the likelihood of developing a trait or disease when a mutation is present. If a gene mutation is highly penetrant, the trait it produces will always or almost always be apparent in a person carrying the altered gene. Relatively few genetic mutations in the genome show high penetrance. Reduced or incomplete penetrance occurs when some people fail to express the trait even though they carry the gene. A gene with low penetrance will only sometimes produce the symptom or trait with which it has been associated at a detectable level. In the case of low penetrance, it is difficult to distinguish influences of environmental factors from those of genetic factors.⁸

The incidence of breast cancer has been associated with a variation in genetic risk factors dependent upon race and cultures. The highest absolute lifetime risk of breast cancer (not the incidence of having a BRCA1 or BRCA2 mutation) is 1 in 8 for non-Hispanic white women, 1 in 14 for African American women, 1 in 21 for New Mexican Hispanics, and 1 in 40 for New Mexican American Indians.⁸ 

Ashkenazi Jews (those with ancestors from Eastern Europe) are 10 times more likely than the general population to carry a BRCA gene mutation. These genetic changes are known as the “founder mutations” because they can be traced back hundreds of years to common ancestors. Women of Ashkenazi Jewish descent and people with a family history of early-onset breast cancer and/or ovarian cancer can benefit from genetic nurse counseling services.¹ (Counselors can be located by ZIP code through the National Society of Genetic Counselors at www.nsgc.org/resourcelink.cfm.)

The risk of breast cancer is greater with an interval of more than 14 years between menarche and first pregnancy. The protection from early pregnancy persists, even in women over age 75, possibly because of changes to breast tissue cells that enhance the ability for DNA repair. Nulliparity, early menarche, and late menopause are also associated with an increased risk for breast cancer.⁸ Since environmental and lifestyle choices can also influence the risk for breast cancer, nurses must consider both genetic predisposition and environmental influences when assessing risk and planning follow-up care for patients and genetic nurse counseling.

Referral: Patients with a family history of breast cancer or ovarian cancer often have questions about genetic testing. Deciding whether to be tested for a genetic disorder can be stressful. To address these concerns, the practitioner can use a family history or pedigree to determine whether patients would benefit from genetic nurse counseling. Practitioners can also use assessment tools for various age groups, available at www.GeneTests.org, to help determine whether patients would benefit from a consultation with a genetic nurse or genetic counselor. The website also has a directory of genetic clinics in each state.

What patients need to know

Patients should meet with a genetic nurse before being tested for mutations in BRCA genes. A genetic nurse counselor can educate patients about BRCA1 or BRCA2 mutations, which are known to cause about 5% to 10% of hereditary breast and ovarian cancers. Nurses can inform patients that 36% to 85% of women with an altered BRCA1 or BRCA2 gene develop breast cancer, depending on the location of the mutation within the gene and the patient’s age, hormones, and childbearing history.⁹ Environmental factors, such as diet, smoking, alcohol use, and exercise, also may influence the genetic susceptibility of breast and ovarian cancer.¹

The penetrance of BRCA1 and BRCA2 mutations is uncertain and probably variable. Nurses can inform patients that breast and ovarian cancer are not a certainty even if a person has the mutation. This uncertainty illustrates the need for more research into the interactions of genes with one another and with the environment, also known as genomics.¹⁰

Ultimately, it’s the patient’s decision whether to undergo genetic testing. The decision may become easier to make once the nurse informs patients about their options for surveillance and treatment of a genetic disease. Some genetic disorders are not treatable, in which case patients may decide to be tested to make decisions about family planning. The decision to be tested for a BRCA mutation may become clear once the nurse and patient discuss the options for people with an increased risk for inheritable breast and ovarian cancer. The patient should know the pros and cons of the conservative approach of increased monitoring for breast or ovarian cancer (i.e., more frequent exams and mammograms) and the more radical choice of prophylactic mastectomy.

The genetic tests for the BRCA mutations can cost several thousand dollars and may not be covered by health insurance. In addition, many people have feared that test results could affect their present and future health insurance coverage. People who have employer-based health insurance have had some protection from the Health Insurance Portability and Accountability Act. HIPAA bars health insurance companies from excluding people from group coverage because of past or present medical problems, including a genetic predisposition to certain diseases. However, HIPAA does not prevent insurance companies from requesting genetic information.¹¹ The Genetic Information Nondiscrimination Act of 2007 (GINA) would provide additional protection. The bill recently gained congressional approval, and President Bush is expected to sign it. GINA would protect people who have had genetic testing against discrimination by health insurance companies and employers.¹²

Education, care, and support: A person who tests positive for a BRCA mutation may feel depressed or fearful. Support groups can help people learn how others have dealt with the knowledge of having a BRCA gene mutation. Nurses can refer patients to the Breast Cancer Options website <www.breastcanceroptions.org> for referrals to support groups, professional counseling, crisis intervention, and clinical and financial resources. Information about the risks of developing breast cancer for patients who have a BRCA mutation is available on the National Cancer Institute website <www.cancer.gov>. The site also has information on the genetics of breast and ovarian cancer. 

Practitioners should encourage parents who have a BRCA mutation to discuss future counseling and genetic testing for their children.

The FVL factor

Another example of how to include genetic competencies in nursing practice involves the FVL mutation.

Assessment: Healthcare providers should complete a family health history for their patients who are considering becoming pregnant. At the first preconception visit, the practitioner can create a pedigree. Disease trends, such as venous thromboembolism (VTE) <www.nurse.com/CE/CE366-60>, can be revealed with a pedigree or family history, which may indicate the need for further evaluation for FVL. An important factor for interpretation of a patient’s family history or pedigree report is that FVL is essentially restricted to Caucasians of European decent.

Identification: The practitioner should consider other  possible genetic-related causes of VTE, such as hemophilia and thrombotic thrombocytopenic purpura. The National Library of Medicine’s Genetics Home Reference site <http://ghr.nlm.nih.gov> has clinical information on many genetic clotting disorders, including FVL thrombophilia. Practitioners can use this information to inform their patients about FVL or other inherited clotting disorders. This module will address the FVL mutation, safety during pregnancy, and genetic inheritance to the child.

FVL, which occurs in 3% to 8% of the population, causes people to stay in a constant state of hypercoagulation as a result of a gene mutation. The mutation causes an increased resistance to aPC, a protein that prevents blood coagulation. FVL is associated with second and third trimester fetal loss, placental abruption, intrauterine growth restriction, and severe preeclampsia.¹³ The normal physiological changes during pregnancy increase several clotting factors, which increase the risk for VTE. Simply stated, pregnancy creates a hypercoagulation state since increased resistance to aPC occurs in all pregnancies during the second and third trimesters. Consequently, pregnant women with FVL have a five- to 16-fold increased risk for VTE compared to nonpregnant women without FVL. Pregnant women with FVL are twice as likely to have a spontaneous abortion than women without FVL.²

Referral: FVL is suspected in patients who have a personal history of thrombosis in pregnancy or of oral contraceptive use or who have a high incidence of family members with unprovoked VTEs. But testing for FVL is complicated by the fact the mutation is relatively common but has low penetrance. Even though they have the mutation, some people may never show symptoms. Many people with FVL never develop thrombosis, and most do not have a VTE until adulthood although some people have recurrent VTE before age 30.²

FVL, like many other genetic mutations, is only partly responsible for patients’ health outcomes. Testing people who have no personal unprovoked VTEs or family history of unprovoked VTEs is not advised since results are not helpful and harmful consequences may be possible, such as denial of prescriptions for oral contraceptives.² A genetic nurse counselor can educate people considering pregnancy on the risks and benefits of FVL genetic testing.¹

Single or double?

Healthcare providers need to understand how genes are inherited and whether a single copy or two copies of the genes in question cause a disorder. In patients who are found to have FVL, healthcare providers need to know whether they have one or two copies of the disease gene because people with two FVL disease genes, one inherited from each parent (homozygous), have more risk for VTE and a worse prognosis than those with one copy (heterozygous). Heterozygous people have one allele that functions normally, which helps reduce the risk of VTEs. Patients considering having children need to know that heterozygous people have a 50% chance of passing the gene to each of their children (autosomal dominant inheritance). One homozygous parent (having two copies of the disease gene) and one parent without the mutation will have all heterozygous offspring.¹ Heterozygosity for FVL, which is more common than homozygosity, has not been associated with an increase in mortality or a reduction in normal life expectancy.²

Education, care, and support: Practitioners should educate patients with FVL about pregnancy risks and the importance of monitoring by a ob/gyn and nurse during and after pregnancy. Prophylactic ante- and postpartum heparin therapy is a consideration for heterozygous and homozygous patients who have FVL and have had a previous unprovoked VTE, i.e., one not due to factors such as extended bed rest or orthopedic injury. Patients need to understand the importance of genetic nurse counseling for their family members who have a history of thrombosis, especially women of childbearing age. Pregnant women who have the FVL mutation and who have previously experienced a spontaneous thromboembolic event appear to have at greater risk of recurrence during pregnancy.² Studies have shown that 44% of women who had a history of VTE during pregnancy tested positive for the FVL mutation. Patients considering pregnancy and who have had a VTE during a previous pregnancy can benefit from genetic counseling.¹²

Stressing prevention

VTE prevention for FVL patients includes advising women with the mutation and a history of venous thrombosis to avoid oral contraceptives and hormone replacement therapy. Patients also need to know the precautions to take while traveling, such as walking and stretching every two hours and avoiding dehydration.² Patients should inform their physicians and surgeons of a positive genetic test for Factor V Leiden; certain situations and conditions increase the risk for developing a VTE, including surgery, a metastatic malignancy, and the use of oral contraceptives.^1,14

Clinical symptoms that patients must report to their provider include pain, swelling, redness, or an area of increased warmth in the lower legs or in the arms. People with FVL have a sixfold increased risk for superficial vein thrombosis, which has the same signs and symptoms as a blood clot but occurs closer to the skin.⁵ Venous leg ulcers occur in a significant number of patients with FVL; however, this complication is more common for FVL homozygote people.²

Surprisingly, a lower incidence of pulmonary embolism exists in patients with a Factor V Leiden DVT than in people without the Leiden mutation. FVL heterozygotes have a nearly eightfold lower incidence of DVT in the iliofemoral veins, the most common source for PE.² Nevertheless, so that patients can recognize this medical emergency, the practitioner should describe the signs and symptoms of PE, such as difficulty breathing, rapid heart rate, chest pain while taking a deep breath, and coughing up blood.⁵ Patients need to know that if symptoms occur, diagnosing a blood clot will require testing, such as ultrasonography, contrast venography, MRI, CT scan, or a blood test known as a D-dimer. (D-dimer is often increased in people with VTE, and a higher-than-normal level may indicate a blood clot.)⁹

Nurses can be the gateway to patient knowledge, assessment, and counseling in this new era of genetics and genomics. Knowing where to find information about genetics and genomics and how to use the information should be goals for all nurses.

For more information, don't forget to click on the 'Sidebars' in the Course Tools section.