Genetic testing looks for specific inherited changes (mutations) in a person’s chromosomes, genes, or proteins. Genetic mutations can have harmful, beneficial, neutral (no effect), or uncertain effects on health. Mutations that are harmful may increase a person’s chance, or risk, of developing a disease such as cancer. Overall, inherited mutations are thought to play a role in about 5 to 10percent of all cancers1.
Genes, mutations, and cancer risk Genetics is the field of science that looks at how traits (such as eye color) are passed down from parents to their children through genes. Genes are located on 23 pairs of long strands of DNA called chromosomes. One of each chromosome pair comes from the mother, and the other from the father. Each chromosome can contain hundreds or thousands of genes that are passed from the parents to the child. Cancer can sometimes appear to “run in families” even if it is not caused by an inherited mutation. Even if a cancer-predisposing mutation is present in a family, it does not necessarily mean that everyone who inherits the mutation will develop cancer.
Genetic testing is the process of using medical tests to look for changes (mutations) in a person’s genes or chromosomes. It’s used to look for gene mutations that might put a person at risk of getting a disease. Genetic testing to learn about your cancer risk is done only if you decide to have it. It’s usually done in families with a history that suggests there’s a disease that may be inherited. The type of testing most often used to check for cancer risk is called predictive gene testing. An example is testing for changes in the BRCA1 and BRCA2 genes (known breast cancer genes) in a woman whose mother and sister had breast cancer 2. If you have any of the following, you might consider genetic testing for yourself:
- Several first-degree relatives (mother, father, sisters, brothers, children) with cancer, especially if they’ve had the same type of cancer.
- Cancers in your family that are sometimes linked to a single gene mutation (for instance, breast, ovarian, and pancreatic cancer).
- Family members who had cancer at a younger age than normal for that type of cancer.
- Close relatives with rare cancers that are linked to inherited cancer syndromes.
- A physical finding that is linked to an inherited cancer (such as having many colon polyps).
- A known genetic mutation in one or more family members who have already had genetic testing.
Genetic testing is also used for other reasons:
- Carrier testing can be used to help couples learn if they carry a gene mutation for a disorder they might pass on to a child, such as cystic fibrosis, sickle-cell anemia, or Tay-Sachs disease.
- Prenatal screening can be used to diagnose some conditions in babies before they are even born, such as Down syndrome.
- Newborn screening is the most widespread form of genetic testing
It is strongly recommended that a person who is considering genetic testing speak with a professional trained in genetics before deciding whether to be tested. These professionals can include doctors, genetic counselors, and other health care providers (such as nurses, psychologists, or social workers). Genetic counseling can help people consider the risks, benefits, and limitations of genetic testing in their particular situation. Sometimes the genetic professional finds that testing is not needed. Genetic tests can reveal information not only about the person being tested but also about that person’s relatives. The presence of a harmful genetic mutation in one family member makes it more likely that other blood relatives may also carry the same mutation. Family relationships can be affected when one member of a family discloses genetic test results that may have implications for other family members. Family members may have very different opinions about how useful it is to learn whether they do or do not have a disease-related genetic mutation. Health discussions may get complicated when some family members know their genetic status while other family members do not choose to know their test results. A conversation with genetics professionals may help family members better understand the complicated choices they may face. For people already diagnosed with cancer, genetic testing of the tumor can often help determine the prognosis (outlook), and can sometimes even help in deciding which treatments will most likely work1.
Genetic testing can have several possible results: positive, negative, true negative, uninformative negative, false negative, variant of unknown significance, or benignpolymorphism. These results are described below1.
- Confirm the diagnosis of a hereditary cancer syndrome
- Indicate an increased risk of developing certain cancer(s) in the future
- Show that someone carries a particular genetic change that does not increase their own risk of cancer but that may increase the risk in their children if they also inherit an altered copy from their other parent (that is, if the child inherits two copies of the abnormal gene, one from their mother and one from their father).
- Suggest a need for further testing
- Provide important information that can help other family members make decisions about their own health care.
Also, people who have a positive test result that indicates that they have an increased risk of developing cancer in the future may be able to take steps to lower their risk of developing cancer or to find cancer earlier, including:
- Being checked at a younger age or more often for signs of cancer
- Reducing their cancer risk by taking medications or having surgery to remove “at-risk” tissue (These approaches to risk reduction are options for only a few inherited cancer syndromes.)
- Changing personal behaviors (like quitting smoking, getting more exercise, and eating a healthier diet) to reduce the risk of certain cancers
A positive result on a prenatal genetic test for cancer risk may influence a decision about whether to continue a pregnancy. The results of pre-implantation testing (performed on embryos created by in vitro fertilization) can guide a doctor in deciding which embryo (or embryos) to implant in a woman’s uterus.
Finally, in patients who have already been diagnosed with cancer, a positive result for a mutation associated with certain hereditary cancer syndromes can influence how the cancer is treated. For example, some hereditary cancer disorders interfere with the body’s ability to repair damage that occurs to cellular DNA. If someone with one of these conditions receives a standard dose of radiation or chemotherapy to treat their cancer, they may experience severe, potentially life-threatening treatment side effects. Knowing about the genetic disorder before treatment begins allows doctors to modify the treatment and reduce the severity of the side effects.
A “negative test result” means that the laboratory did not find the specific alteration that the test was designed to detect. This result is most useful when working with a family in which the specific, disease-causing genetic alteration is already known to be present. In such a case, a negative result can show that the tested family member has not inherited the mutation that is present in their family and that this person therefore does not have the inherited cancer syndrome tested for, does not have an increased genetic risk of developing cancer, or is not a carrier of a mutation that increases cancer risk. Such a test result is called a “true negative.” A true negative result does not mean that there is no cancer risk, but rather that the risk is probably the same as the cancer risk in the general population.
When a person has a strong family history of cancer but the family has not been found to have a known mutation associated with a hereditary cancer syndrome, a negative test result is classified as an “uninformative negative” (that is, does not provide useful information). It is not possible to tell whether someone has a harmful gene mutation that was not detected by the particular test used (a “false negative”) or whether the person truly has no cancer-predisposing genetic alterations in that gene. It is also possible for a person to have a mutation in a gene other than the gene that was tested.
If genetic testing shows a change that has not been previously associated with cancer in other people, the person’s test result may report “variant of unknown significance,” or VUS. This result may be interpreted as “ambiguous” (uncertain), which is to say that the information does not help in making health care decisions.
If the test reveals a genetic change that is common in the general population among people without cancer, the change is called a polymorphism. Everyone has commonly occurring genetic variations (polymorphisms) that are not associated with any increased risk of disease.
A genetic counselor, doctor, or other health care professional trained in genetics can help an individual or family understand their test results. Such counseling may include discussing recommendations for preventive care and screening with the patient, referring the patient to support groups and other information resources, and providing emotional support to the person receiving the results.
Research to find newer and better ways of detecting, treating, and preventing cancer in people who carry genetic mutations that increase the risk of certain cancers is ongoing. Scientists are also doing studies to find additional genetic changes that can increase a person’s risk of cancer.
- National Cancer Institute. Genetic Testing for Hereditary Cancer Syndromes. Accessed at http://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-fact-sheet on June 29, 2015.
American Cancer Society. Genetic Testing for Cancer. Accessed at http://www.cancer.org/acs/groups/cid/documents/webcontent/002548-pdf.pdf on June 29, 2015.