What is genetic testing?

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 gland tumors

Multiple endocrine neoplasia type 2

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 counseling is 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 benignpolymorphism. 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.


Email motherhealth@gmail.com for a DNA test for early cancer detection.

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