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.
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. The types of tumors most frequently seen in LFS include bone and soft tissue cancers (called “sarcomas”,), breast cancer, brain tumors, and cancer of the adrenal gland. The diagnosis of LFS is based on an individual’s personal and family history of cancers.
- Inherited mutations in the BRCA1and 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.
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.
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.
