What is genetic testing?

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 10 percent of all cancers.

Cancer can sometimes appear to “run in families” even if it is not caused by an inherited mutation. For example, a shared environment or lifestyle, such as tobacco use, can cause similar cancers to develop among family members. However, certain patterns—such as the types of cancer that develop, other non-cancer conditions that are seen, and the ages at which cancer typically develops—may suggest the presence of a hereditary cancer syndrome.

The genetic mutations that cause many of the known hereditary cancer syndromes have been identified, and genetic testing can confirm whether a condition is, indeed, the result of an inherited syndrome. Genetic testing is also done to determine whether family members without obvious illness have inherited the same mutation as a family member who is known to carry a cancer-associated mutation.

Inherited genetic mutations can increase a person’s risk of developing cancer through a variety of mechanisms, depending on the function of the gene. Mutations in genes that control cell growth and the repair of damaged DNA are particularly likely to be associated with increased cancer risk.


Does someone who inherits a cancer-predisposing mutation always get cancer?

No. 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. Several factors influence the outcome in a given person with the mutation.

One factor is the pattern of inheritance of the cancer syndrome. To understand how hereditary cancer syndromes may be inherited, it is helpful to keep in mind that every person has two copies of most genes, with one copy inherited from each parent. Most mutations involved in hereditary cancer syndromes are inherited in one of two main patterns: autosomal dominant and autosomal recessive.

With autosomal dominant inheritance, a single altered copy of the gene is enough to increase a person’s chances of developing cancer. In this case, the parent from whom the mutation was inherited may also show the effects of the gene mutation. The parent may also be referred to as a carrier.

With autosomal recessive inheritance, a person has an increased risk of cancer only if he or she inherits a mutant (altered) copy of the gene from each parent. The parents, who each carry one copy of the altered gene along with a normal (unaltered) copy, do not usually have an increased risk of cancer themselves. However, because they can pass the altered gene to their children, they are called carriers.

A third form of inheritance of cancer-predisposing mutations is X-linked recessive inheritance. Males have a single X chromosome, which they inherit from their mothers, and females have two X chromosomes (one from each parent). A female with a recessive cancer-predisposing mutation on one of her X chromosomes and a normal copy of the gene on her other X chromosome is a carrier but will not have an increased risk of cancer. Her sons, however, will have only the altered copy of the gene and will therefore have an increased risk of cancer.

Even when people have one copy of a dominant cancer-predisposing mutation, two copies of a recessive mutation, or, for males, one copy of an X-linked recessive mutation, they may not develop cancer. Some mutations are “incompletely penetrant,” which means that only some people will show the effects of these mutations. Mutations can also “vary in their expressivity,” which means that the severity of the symptoms may vary from person to person.

What genetic tests are available for cancer risk?

More than 50 hereditary cancer syndromes have been described. The majority of these are caused by highly penetrant mutations that are inherited in a dominant fashion. The list below includes some of the more common inherited cancer syndromes for which genetic testing is available, the gene(s) that are mutated in each syndrome, and the cancer types most often associated with these syndromes. 


​Her sons, however, will have only the altered copy of the gene and will therefore have an increased risk of cancer.

Even when people have one copy of a dominant cancer-predisposing mutation, two copies of a recessive mutation, or, for males, one copy of an X-linked recessive mutation, they may not develop cancer. Some mutations are “incompletely penetrant,” which means that only some people will show the effects of these mutations. Mutations can also “vary in their expressivity,” which means that the severity of the symptoms may vary from person to person.

What genetic tests are available for cancer risk?

More than 50 hereditary cancer syndromes have been described. The majority of these are caused by highly penetrant mutations that are inherited in a dominant fashion. The list below includes some of the more common inherited cancer syndromes for which genetic testing is available, the gene(s) that are mutated in each syndrome, and the cancer types most often associated with these syndromes. 

Hereditary breast cancer and ovarian cancer syndrome

Genes: BRCA1, BRCA2
Related cancer types: Female breast, ovarian, and other cancers, including prostate, pancreatic, and male breast cancer

Li-Fraumeni syndrome

Gene: TP53
Related cancer types: Breast cancer, soft tissue sarcoma, osteosarcoma (bone cancer), leukemia, brain tumors, adrenocortical carcinoma (cancer of the adrenal glands), and other cancers

Cowden syndrome (PTEN hamartoma tumor syndrome)

Gene: PTEN
Related cancer types: Breast, thyroid, endometrial (uterine lining), and other cancers

Lynch syndrome (hereditary nonpolyposis colorectal cancer)

Genes: MSH2, MLH1, MSH6, PMS2, EPCAM
Related cancer types: Colorectal, endometrial, ovarian, renal pelvis, pancreatic, small intestine, liver and biliary tract, stomach, brain, and breast cancers

Familial adenomatous polyposis

Gene: APC
Related cancer types: Colorectal cancer, multiple non-malignant colon polyps, and both non-cancerous (benign) and cancerous tumors in the small intestine, brain, stomach, bone, skin, and other tissues

Retinoblastoma

Gene: RB1
Related cancer types: Eye cancer (cancer of the retina), pinealoma (cancer of the pineal gland), osteosarcoma, melanoma, and soft tissue sarcoma

Multiple endocrine neoplasia type 1 (Wermer syndrome)

Gene: MEN1
Related cancer types: Pancreatic endocrine tumors and (usually benign) parathyroid and pituitary glandtumors

Multiple endocrine neoplasia type 2

Gene: RET
Related cancer types: Medullary thyroid cancer and pheochromocytoma (benign adrenal gland tumor)

Von Hippel-Lindau syndrome

Gene: VHL
Related cancer types: Kidney cancer and multiple noncancerous tumors, including pheochromocytoma

Who should consider genetic testing for cancer risk?

Many experts recommend that genetic testing for cancer risk should be strongly considered when all three of the following criteria are met:

The person being tested has a personal or family history that suggests an inherited cancer risk condition
The test results can be adequately interpreted (that is, they can clearly tell whether a specific genetic change is present or absent)
The results provide information that will help guide a person’s future medical care

The features of a person’s personal or family medical history that, particularly in combination, may suggest a hereditary cancer syndrome include:

Cancer that was diagnosed at an unusually young age
Several different types of cancer that have occurred independently in the same person
Cancer that has developed in both organs in a set of paired organs, such as both kidneys or both breasts
Several close blood relatives that have the same type of cancer (for example, a mother, daughter, and sisters with breast cancer)
Unusual cases of a specific cancer type (for example, breast cancer in a man)
The presence of birth defects, such as certain noncancerous (benign) skin growths or skeletal abnormalities, that are known to be associated with inherited cancer syndromes
Being a member of a racial/ethnic group that is known to have an increased chance of having a certain hereditary cancer syndrome and having one or more of the above features as well

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 counseling includes a detailed review of the individual’s personal and family medical history related to possible cancer risk. Counseling also includes discussions about such issues as:

Whether genetic testing is appropriate, which specific test(s) might be used, and the technical accuracy of the test(s)
The medical implications of a positive or a negative test result (see below)
The possibility that a test result might not be informative—that is, that the information may not be useful in making health care decisions (see below)
The psychological risks and benefits of learning one’s genetic test results
The risk of passing a genetic mutation (if one is present in a parent) to children

Learning about these issues is a key part of the informed consent process. Written informed consent is strongly recommended before a genetic test is ordered. People give their consent by signing a form saying that they have been told about, and understand, the purpose of the test, its medical implications, the risks and benefits of the test, possible alternatives to the test, and their privacy rights.

Unlike most other medical tests, 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.

How is genetic testing done?

Genetic tests are usually requested by a person’s doctor or other health care provider. Although it may be possible to obtain some genetic tests without a health care provider’s order, this approach is not recommended because it does not give the patient the valuable opportunity to discuss this complicated decision with a knowledgeable professional.

Testing is done on a small sample of body fluid or tissue—usually blood, but sometimes saliva, cells from inside the cheek, skin cells, or amniotic fluid (the fluid surrounding a developing fetus).

The sample is then sent to a laboratory that specializes in genetic testing. The laboratory returns the test results to the doctor or genetic counselor who requested the test. In some cases, the laboratory may send the results to the patient directly. It usually takes several weeks or longer to get the test results. Genetic counselingis recommended both before and after genetic testing to make sure that patients have accurate information about what a particular genetic test means for their health and care.

What do the results of genetic testing mean?

Genetic testing can have several possible results: positive, negative, true negative, uninformative negative, false negative, variant of unknown significance, or benign polymorphism. These results are described below.

A “positive test result” means that the laboratory found a specific genetic alteration (or mutation) that is associated with a hereditary cancer syndrome. A positive result may:

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.

Who can help people understand their test results?

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.

In some cases, a genetic counselor or doctor may recommend that other family members consider being tested for specific gene changes that indicate an increased risk of cancer. The decision to test other family members is complicated. It requires a careful evaluation of family history and other factors as well as advice from a genetic counselor or other professional trained in genetics. In general, physicians rely on the family member who has been tested to share the genetic information with their relatives so that family members will know that a genetic condition has been identified in their family. Then, each family member will need to make their own decision regarding whether or not to be tested themselves.

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