Genetic tests analyze an individual’s blood or bone marrow for mutations and variations in genes that may indicate an increased risk for developing a disease or disorder. The tests may be an effective diagnostic tool in patients who have a family history of some types of cancer. According to the National Cancer Institute, gene testing has been effective in detecting an inherited susceptibility to breast, colon, ovarian and thyroid cancers.

Predictive gene tests have been developed by scientists to detect certain gene flaws that have been associated with a higher risk of some cancers. An accurate gene test can indicate that a person has a genetic mutation but it cannot determine if the individual will actually develop the disease. However, genetic testing continues to show great promise. Countless lives may be saved once scientists fully harness the power of genetic testing and apply it to cancer screening, treatment and prevention.

However, there are many questions about testing that remain unanswered. Patients should be aware that these tests are not 100 percent reliable and that there are limits to what they can predict. There are also concerns about how positive results in genetic testing might impact a patient’s ability to get a job or obtain health and life insurance.

All types of cancer involve genes. Cancer begins when cells grow uncontrollably and this growth is controlled or not controlled by instructions from the genes. When genes are damaged, or mutated, these instructions may be incorrect or incomplete and lead to tumor formation.

Genetic testing is used by physicians to predict or diagnose genetic disorders that are caused by gene mutations. The tests typically use blood samples, but also may be conducted with bone marrow, skin or other tissues. These tests can analyze a patient's:

• DNA (deoxyribonucleic acid). The genetic material that houses instructions for all of the body’s chemical processes.
  
  
• RNA (ribonucleic acid). The genetic material that converts the information stored in DNA into proteins.
  
  
• Proteins. Molecules composed of amino acids that serve as the basis of body structures, such as hair and skin.
  
  
• Chromosomes. Rod-shaped elements in the nucleus of each cell. Chromosomes contain DNA and proteins that comprise the genes that carry hereditary information.
  
  
• Metabolites. Any product of metabolism.

Genes are inherited from both the mother’s egg and the father’s sperm. Genetic tests are most often used to determine if an individual has inherited a gene alteration known to be associated with cancer, or to confirm a suspected genetic mutation.

Genes provide the basic blueprint for an individual’s development, growth and bodily functions. Everything from eye color to height and body build is largely controlled by genetics, although environmental factors also play a role in the development of physical characteristics.

Genes are normally reproduced whenever cells divide, with new cells sharing the same genetic makeup as their predecessors. However, in some cases, an error occurs that causes the new gene to have an abnormality – or mutation – in its genetic code. Mutations can have harmful, beneficial or neutral effects on health. It is these mutations that may eventually lead to cancer. Scientists have not yet identified all of the genes in the human body (human genome) or the purpose of each gene.

In most cases, genetic mutations are due to the aging of the cell, or environmental or behavioral factors. These are known as acquired mutations. However, 5 to 10 percent of cancers are caused by hereditary mutations, according to the American Cancer Society (ACS). Diseases such as cancer may occur if a person has a dominant disease gene, two recessive genes for the disease, or mutations that interact with each other or the environment. The body has two main types of genes that influence cancer risk:

• Oncogenes are acquired or hereditary mutations that cause normal cells to grow out of control. In normal function, these genes direct cell growth. When their DNA is damaged or mutated, they stay “turned on” and tell a cell to continue to grow without stopping. In such situations, the oncogene may promote the growth of a tumor.  
  
  
• Tumor suppressor genes are normal, helpful genes that control cell division, repair damaged DNA and destroy cells that cannot be repaired. Acquired or hereditary mutations can inactivate tumor suppressor genes, which means they do not stop cell growth and a tumor may develop. Inherited abnormalities of tumor suppressor genes cause many of the hereditary cancers.

Researchers have identified more than 100 oncogenes and about 30 tumor suppressor genes and continue their attempts to discover more of these genes. Scientists are only beginning to understand the complexity of the genetic aspects of cancer. Cancers associated with congenital (inborn)  genetic disorders are grouped under the heading hereditary cancer syndromes. They include:

• Hereditary breast and ovarian cancer (HBOC). About 5 to 10 percent of breast cancers are associated with mutated genes, primarily the BRCA1 and BRCA2 genes. Two other genes, CHEK2 and TP53, have also been linked to breast cancer. The presence of these genes indicates an increased risk of ovarian cancer as well. Women with a BRCA1/2 mutation are 3 to 7 times more likely to develop breast cancer than those without the gene alteration. In the general population, a woman has 1.7 percent chance of developing ovarian cancer in her lifetime. If a woman has a BRCA1/2 gene mutation, the risk increases to 16 to 60 percent.
  
  
• Familial prostate cancer.  Male carriers of the two main gene mutations (BRCA1/2) involved in hereditary breast cancer have three to four times the risk of developing prostate cancer. Other gene mutations, including the PITX2 gene. have also been implicated in prostate cancer,
  
  
• Hereditary causes of colorectal cancer, including hereditary nonpolyposis colon cancer (HNPCC) and familial adenomatous polyposis (FAP). These conditions, characterized by polyps that may become malignant, are estimated to account for up to 15 percent of cases of colorectal cancer.
  
  
• Familial melanoma. Several melanoma-predisposing autosomal dominant genes have been identified. An estimated 5 to 7 percent of people with melanoma come from genetically high-risk families.
  
  
• Neurofibromatosis. Type 1 neurofibromatosis affects one person in 4,000 and involves skin discoloration and tumors that become malignant in up to 5 percent of cases. Type 2 affects one person in 50,000 and often affects the acoustic nerve.
  
  
• Fanconi’s anemia. An autosomal recessive (health effect of mutation is caused only when copies of the mutation are inherited from both parents) condition associated with about 20 percent of cases of childhood aplastic anemia. It is more common in Ashkenazi Jews.

Even in cancers that can be linked to environmental conditions, such as exposure to tobacco smoke or radiation, the environment damages the tissue and genetic material to initiate the tumor growth. The genetic risk associated with cancers lies in the inheritance or mutation of genes that make a person more likely to develop a certain type of cancer. In this sense, all cancers are genetic. Some types of cancer can occur in families with above-average frequency. However, this does not mean a hereditary mutation is involved. Genetic mutations can harm, have no effect on or even help a person’s health. The cells usually but not always recognize and repair acquired mutations.

Recently, researchers have completed a “map” of the genes associated with breast and colon cancer tumors. After analyzing more than 13,000 genes from tumors, the study showed that each type of cancer had about 100 different genes with mutations. Continuing research to identify which mutations affect cancer may provide information about effective treatment and new types of therapies to repair the gene damage or stop the progress of the cancer.

Patients may want to consider genetic testing if they have a:

• Family history of cancer, especially:
  
  
• Clustering of the same type of cancer in close relatives (parents, siblings, children)
  
  
• Two or more primary cancers in one relative
  
  
• Patterns of cancer in the family that are associated with a known cancer syndrome or with other diseases
  
  
• Previous individual history of cancer
  
  
• Concerns about family members being at risk for cancer

This information may be used to help determine whether a family may have a hereditary cancer syndrome, what the most likely diagnosis is if a syndrome is indicated, and how the genetic traits are passed down in the family (dominant, recessive or X-linked). Answering these questions can help individuals make a more informed decision on whether to undergo genetic tests and genetic counseling.

Depending on the type of cancer, patients who receive positive genetic test results have several options. These include:

• Screening at earlier age
  
  
• More frequent screening schedule
  
  
• More in-depth tests recommended for high-risk patients
  
  
• Taking preventative medications (e.g. hormone-blocking drugs)
  
  
• Making certain lifestyle changes (e.g. changing an unhealthy diet or quitting smoking)
  
  
• Having preventative surgery, such as mastectomy  for women with a gene mutation for breast cancer

Genetic testing, like most medical procedures, has its associated benefits and risks. On the one hand, a predictive gene test can help determine a patient’s risk of future cancer. Therefore, individuals who test positive for genes associated with cancer can be monitored closely for early detection and treatment of a disease.

In other cases, patients who test positive may be urged to take preventative measures that can lower the risk of future cancers. For example, women who test positive for the genetic mutations BRCA1 or BRCA2 are at high risk for developing breast cancer. Some patients may choose to have a mastectomy (called a prophylactic mastectomy) to reduce their risk of developing breast cancer. 

With genetic testing, there is also the risk that individuals with negative test results may adopt a false sense of security, as seen with breast cancer.  Most breast cancers occur in women who would test negative for breast cancer mutations.

These tests also fail to reveal the exact type or severity of cancer that may develop and how it will progress. In addition, technical or human errors can skew testing results, and some tests will be inconclusive even when properly performed. In a recent study conducted on commercial genetic testing, the American Cancer Society reported that up to 12 percent of people who tested negative for BRCA1 and BRCA2 gene mutations may have had dangerous alterations in those genes. According to ACS, a woman with no BRCA mutations has about a 13 percent lifetime risk of breast cancer. In contrast, a woman with a mutation has an 80 percent lifetime risk of developing breast cancer. For this reason, it is important that genetic testing be as accurate as possible.

Although patients can often benefit from genetic testing, these diagnostic tools do raise social, ethical and legal concerns that they should consider before choosing to be tested. Genetic testing does not necessarily tell patients whether or not they (or their children) will develop cancer or other diseases. Negative results do not ensure that the patient will never develop cancer, and positive results do not indicate when cancer is likely to occur, if it occurs at all.

Genetic counseling is the process in which a healthcare provider informs the patient about all aspects of genetic testing and the potential impact of the test results. Genetic counselors are professionals who have earned a master’s degree in medical genetics and counseling skills, and who have passed a certification examination administered by the American Board of Genetic Counseling. Their role includes:

• Evaluating the patient’s family history and medical history
  
  
• Assessing the patient's understanding of tests and implications of results
  
  
• Ordering appropriate genetic tests
  
  
• Explanation of the testing process and anticipated costs
  
  
• Evaluating test results
  
  
• Conveying testing information to patients
  
  
• Advising patient of available options
  
  
• Determining additional testing for patient or family members

It is important to note that the American Cancer Society (ACS) recommends that patients speak with a trained genetic counselor about the following prior to genetic testing:

• Benefits and risks of testing. It is important for patients to determine the value of the information that can be obtained from genetic testing. The benefits for the patient and other family members should be weighed against the potential risks.
  
  
• Privacy of genetic testing results. Patients should be assured that measures will be taken to ensure the confidentiality of all results. However, test results often go into the patient’s medical records, which may be accessed by insurance companies or other health professionals.


• Effect of test results on the patient’s ability to obtain and keep life, disability and health insurance. There is significant concern that patients who have positive test results will be unable to acquire medical coverage, or will have to pay substantially higher premiums. Federal and state law offers some protections, but these safeguards do not apply to all patients and situations.
  
  
• Effect of test results on current and future employment. In some cases, employers may have the right to examine an employee’s medical records.
  
  
• Anticipated costs. Patients should be provided with information about the out-of-pocket expenses. Their expenses will vary depending on the number of tests, type of test and insurance coverage.
  
  
• Medicines, surgery or other treatments that may lower cancer risks in patients whose test results indicate high genetic cancer risk.

Many different body fluids or tissues can be used during genetic testing, including blood, skin, urine, semen, bone or other tissues. All types of genetic testing must be ordered by a physician and the tests may be completed in a number of locations, such as a commercial laboratory or hospital. Genetic testing involves one or more of the following methods:

• DNA (deoxyribonucleic acid) testing. The sample is analyzed in a laboratory using molecular probes that examine the length of individual DNA molecules and check for a specific coding sequence. Usually, the technician will look for sequences associated with cancer or other serious diseases. DNA testing may focus on a specific gene mutation, a panel of mutations or the complete gene sequence.
  
  
• Cytogenic testing. Analyzes chromosomes for proper structure and arrangement, as well as any abnormalities.
  
  
• Biochemical testing. Examines whether any proteins or enzymes produced by cells are missing. Special preparations, such as fasting or not eating certain foods, may be required before testing.

Genetic testing is available for gene mutations associated with a number of cancers. The most commonly used genetic tests are conducted for:

• Breast cancer. Variations of several genes increase the risk of developing breast cancer. BRCA1 and BRCA2 genes are the primary genes related to hereditary breast cancer and ovarian cancer. If an individual tests positive for an altered BRCA1/2 gene, it is called a "known mutation."  The person has inherited a BRCA mutation and has an increased risk of developing breast and ovarian cancer. In addition, the person has a chance of passing the alteration on to their children.
  
  There are inherited changes in several other genes that have been associated with increased breast cancer risk. These include CHEK2, ATM, BRIP1 and RAD51.  Some studies have also found certain mutations of the AR gene may raise the risk of breast cancer while other research has not shown this connection. Some mutations, known as somatic mutations, are not inherited but acquired during a person's lifetime. Somatic mutations associated with breast cancer include TP53, DIRAS3 and ERBB2 (also known as Her-2/neu). Genetic tests can identify these mutations and help with prediction of cancer as well as prevention options and treatment planning.
  
  In February 2007, the U.S. Food and Drug Administration (FDA) approved of a new genetic test for breast cancer. The test, called MammaPrint, can help determine the likelihood that early stage breast cancer will return within five to 10 years after treatment. It measures the activity of 70 genes from breast cancer tissue, which can provide information about the risk of cancer spreading to another site. The test can help physicians decide whether a breast cancer patient should receive chemotherapy as part of treatment for early stage disease.
  
  Many gene tests for breast cancer are being evaluated in research studies and clinical trials. Researchers have developed two genomic tests to help better predict how patients will respond to hormone therapy or chemotherapy. One test uses a genomic indicator to predict the 10-year survival rate for patients who receive postoperative hormonal therapy with the drug tamoxifen. The second test analyzes 780 different gene combinations to predict a breast cancer patient's response to chemotherapy.
  
  
• Ovarian cancer. Physical examinations and screening tests are not effective in detecting ovarian cancer in the early stages. For that reason, researchers have focused on developing genetic tests to help predict and identify the disease. The tests examine genes, gene expression levels, proteins and tumor markers. As with breast cancer, BRCA1 and BRCA2 mutations have been associated with an increased risk of ovarian cancer. In addition, elevated levels of the tumor marker CA-125 have been linked to ovarian cancer. Other genes are being analyzed for their association to ovarian cancer in research studies and clinical trials.
  
  
• Colon cancer. Inherited forms of colon cancer account for only about 5 percent of these cancers. However, individuals who have a close relative with colon cancer have twice the risk of developing the disease. Genetic testing may be considered by high risk individuals to identify genetic syndromes associated with the colon cancer. Gene mutations are responsible for family adenomatous polyposis (FAP) and Lynch Syndrome, conditions closely associated with colon cancer.
  
  
• Lung cancer. Researchers are studying several genetic tests that may help predict the development of lung cancer, the effectiveness of certain treatments and methods to prevent the disease. Scientists have found that the activity level of two genes, called RRM1 and ERCC1, can help predict the benefit of chemotherapy in lung cancer patients. High activity suggests that a lung cancer patient would do better without post-operative chemotherapy while low activity showed a need for chemo treatment. Other studies have focused on smoker's genes and their ability to repair DNA.

The results from genetic testing are returned from the laboratory to the patient’s physician. The physician and or/genetic counselor will schedule a meeting with the patient to discuss the findings and any follow-up steps, if necessary. Depending on the nature of the testing, patients may have to wait several weeks to several months for results.

When genetic tests are analyzed, three primary factors are considered:

• Analytical validity. How well the test measures the property or characteristic it is supposed to measure.
  
  
• Clinical validity. The likelihood that a cancer, or other disease, will develop in someone with a positive test result.
  
  
• Clinical utility. The likelihood a test will result in an improved health outcome by prompting an intervention.

A positive genetic test result means the patient is more likely than the average person to develop the cancer associated with the mutation. However, it does not mean the patient or that individual's children will definitely get the disease. The likelihood of developing the cancer is based on the genetic mutation and its link to the specific cancer.

If an individual tests positive for a gene mutation, there are several approaches that may be considered. There is limited data available for the effectiveness of these approaches in preventing cancer. Patients should discuss their options with their physicians and genetic counselors. These approaches include:

• Surveillance. Careful monitor by the patients themselves and appropriate physicians may help detect the cancer at an earlier stage. For example, individuals who test positive for BRCA1/2 alterations may undergo mammograms more frequently or at an earlier age. They also may be monitored with transvaginal ultrasounds and CA-125 testing for ovarian cancer prevention.
  
  
• Prophylactic surgery. This type of preventive surgery involves removing at-risk tissue to reduce the risk of developing cancer. These types of surgeries include preventive mastectomy (removal of healthy breasts) or oophorectomy (removal of healthy ovaries). Not all at-risk tissue can be removed and patients can still develop associated cancers (e.g. breast or ovarian cancer).
  
  
• Risk avoidance. Individuals may change lifestyle habits to reduce the risk of their cancer. Those who have mutations associated with breast cancer may increase their physical activity and maintain a healthy weight. Individuals who test positive for colorectal cancer gene mutations may choose to reduce red meat in their diets and eat more grains and fiber.
  
  
• Chemoprevention.  This approach uses natural or synthetic substances to lower the risk of developing cancer or help prevent its recurrence. Some studies have found that certain hormone-blocking drugs can reduce the risk of invasive breast cancer in women at higher risk for developing the disease. However, there have been limited studies on the use of chemoprevention in women with BRCA1/2 mutations. Additional studies are being considered for the use of hormone-blocking drugs for individuals with these altered genes.

A negative genetic test result does not mean the individual will not develop the cancer, but simply indicates that the patient may be no more likely to develop the disease than the average person with no inherited risk. However, it is possible that the patient may have another family mutation that has gone undetected. In addition, genetic tests do not detect all mutations that can cause a disease and some mutations are still being investigated for their connection to cancer.

Preparing questions in advance can help patients to have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor or healthcare professional the following questions about genetic testing:

1. Which genetic tests, if any, should I consider based on my family history?
   
   
2. What is involved in the recommended test?
   
   
3. Where can I have the test completed?
   
   
4. What can I expect to learn from the genetic test?
   
   
5. How accurate is the test?
   
   
6. When can I expect to receive the results?
   
   
7. Who will review the results with me?
   
   
8. What are the benefits and risks of undergoing the test?
   
   
9. Who will have access to my test results?
   
   
10. What is the cost of the testing?
    
    
11. Will insurance cover the cost of the test? If so, do I want to use insurance coverage?
    
    
12. How could the testing affect my health or life insurance?
    
    
13. What steps should I consider if my test is positive?
    
    
14. Should any other family members undergo genetic testing?