Cancer is a genetic disease—that is, cancer is caused by certain changes to genes that control the way our cells function, especially how they grow and divide. These changes include mutations in the DNA that makes up our genes.
Genetic changes that increase cancer risk can be inherited from our parents if the changes are present in germ cells, which are the reproductive cells of the body (eggs and sperm). Such changes, called germline changes, are found in every cell of the offspring.
Cancer-causing genetic changes can also be acquired during one’s lifetime, as the result of errors that occur as cells divide during a person’s lifetime or exposure to substances, such as certain chemicals in tobacco smoke, and radiation, such as ultraviolet rays from the sun, that damage DNA.
Genetic changes that occur after conception are called somatic (or acquired) changes. They can arise at any time during a person’s life. The number of cells in the body that carry such changes depends on when the changes occur during a person’s lifetime.
In general, cancer cells have more genetic changes than normal cells. But each person’s cancer has a unique combination of genetic alterations. Some of these changes may be the result of cancer, rather than the cause. As the cancer continues to grow, additional changes will occur. Even within the same tumor, cancer cells may have different genetic changes.
Hereditary Cancer Syndromes
Inherited genetic mutations play a major role in about 5 to 10 percent of all cancers. Researchers have associated mutations in specific genes with more than 50 hereditary cancer syndromes, which are disorders that may predispose individuals to developing certain cancers.
Genetic tests can tell whether a person from a family that shows signs of such a syndrome has one of these mutations. These tests can also show whether family members without obvious disease have inherited the same mutation as a family member who carries a cancer-associated mutation. (For more information, see this overview of genetic testing for hereditary cancer syndromes.)
Many experts recommend that genetic testing for cancer risk be considered when someone has a personal or family history that suggests an inherited cancer risk condition, as long as the test results can be adequately interpreted (that is, they can clearly tell whether a specific genetic change is present or absent) and when the results provide information that will help guide a person’s future medical care.
Cancers that are not caused by inherited genetic mutations can sometimes appear to “run in families.” For example, a shared environment or lifestyle, such as tobacco use, can cause similar cancers to develop among family members. However, certain patterns in a family—such as the types of cancer that develop, other non-cancer conditions that are seen, and the ages at which cancer develops—may suggest the presence of a hereditary cancer syndrome.
Even if a cancer-predisposing mutation is present in a family, not everyone who inherits the mutation will necessarily develop cancer. Several factors influence the outcome in a given person with the mutation, including the pattern of inheritance of the cancer syndrome.
Here are examples of genes that can play a role in hereditary cancer syndromes.
- The most commonly mutated gene in all cancers is TP53, which produces a protein that suppresses the growth of tumors. In addition, germline mutations in this gene can cause Li-Fraumeni syndrome, a rare, inherited disorder that leads to a higher risk of developing certain cancers.
- Inherited mutations in the BRCA1 and BRCA2 genes are associated with hereditary breast and ovarian cancer syndrome, which is a disorder marked by an increased lifetime risk of breast and ovarian cancers in women. Several other cancers have been associated with this syndrome, including pancreatic and prostate cancers, as well as male breast cancer.
- Another gene that produces a tumor suppressor protein is PTEN. Mutations in this gene are associated with Cowden syndrome, an inherited disorder that increases the risk of breast, thyroid, endometrial, and other types of cancer.
For more genes that can play a role in hereditary cancer syndromes, see Genetic Testing for Hereditary Cancer Syndromes.
Genetic Test Results
Genetic tests are usually requested by a person’s doctor or other health care provider. Genetic counseling can help people consider the risks, benefits, and limitations of genetic testing in their particular situations.
The results of genetic tests can be positive, negative, or uncertain. A genetic counselor, doctor, or other health care professional trained in genetics can help an individual or family understand their test results. These professionals can also help explain the incidental findings that a test may yield, such as a genetic risk factor for a disease that is unrelated to the reason for administering the test. And they can clarify the implications of test results for other family members.
Medical test results are normally included in a person’s medical records, particularly if a doctor or other health care provider has ordered the test or has been consulted about the test results. Therefore, people considering genetic testing should understand that their results may become known to other people or organizations that have legitimate, legal access to their medical records, such as their insurance company or employer, if their employer provides the patient’s health insurance as a benefit.
However, legal protections are in place to prevent genetic discrimination. The Genetic Information Nondiscrimination Act of 2008 is a federal law that prohibits discrimination based on genetic information in determining health insurance eligibility or rates and suitability for employment. In addition, because a person’s genetic information is considered health information, it is covered by the Privacy Rule of the Health Information Portability and Accountability Act of 1996.
Clinical DNA Sequencing
Until recently, most genetic testing for cancer focused on testing for individual inherited mutations. But, as more efficient and cheaper DNA sequencing technologies have become available, sequencing of an individual’s entire genome or the DNA of an individual’s tumor is becoming more common.
Clinical DNA sequencing can be useful in detecting many genetic mutations at one time. Targeted multiple-gene panels test for many inherited mutations or somatic mutations at the same time. These panels can include different genes and be tailored to individual tumor types. Targeted gene panels limit the data to be analyzed and include only known genes, which makes the interpretation more straightforward than in broader approaches that assess the whole genome (or tumor genome) or significant parts of it. Multiple-gene panel tests are becoming increasingly common in genetic testing for hereditary cancer syndromes.
Tumor sequencing can identify somatic mutations that may be driving the growth of particular cancers. It can also help doctors sort out which therapies may work best against a particular tumor. For instance, patients whose lung tumors harbor certain mutations may benefit from drugs that target these particular changes.
Testing tumor DNA may reveal a mutation that has not previously been found in that tumor type. But if that mutation occurs in another tumor type and a targeted therapy has been developed for the alteration, the treatment may be effective in the “new” tumor type as well.
Tumor sequencing can also identify germline mutations. Indeed, in some cases, the genetic testing of tumors has shown that a patient’s cancer could be associated with a hereditary cancer syndrome that the family was not aware of.
As with testing for specific mutations in hereditary cancer syndromes, clinical DNA sequencing has implications that patients need to consider. For example, they may learn incidentally about the presence of germline mutations that may cause other diseases, in them or in their family members.