What is a cancer predisposition syndrome?

Our genes, made up of specific sequences of DNA, program cells to function correctly. Each cell has two copies of most genes, one inherited from each parent. Sometimes, one or both copies of a gene are changed, leading to cells not functioning right. These changes or variations (sometimes referred to as mutations) may lead to a higher risk of cancer development, which is called a cancer predisposition syndrome.

Diagnosing a cancer predisposition syndrome

To diagnose a cancer predisposition syndrome, a doctor or genetic counselor will ask questions about a person’s medical history, as well as the medical history of close and distant relatives, with special attention to cancer history. They will create a family tree (also called a “pedigree”) and determine if the pattern matches what is seen with specific cancer predisposition syndromes.

Genetic testing for cancer predisposition syndromes

If a specific syndrome or group of syndromes is suspected in a person or family, the doctor or genetic counselor may suggest genetic testing, for one gene, a group of genes, or all of the genes in the body. Genetic testing can be performed from blood, saliva, and a few other sample types. The DNA is isolated from the sample and the sequence of the DNA is determined and compared to what is considered to be the normal sequence.

Possible results. Differences in the sequence of a gene that are known or thought to cause it to function improperly are called pathogenic or likely pathogenic variants and may confirm the diagnosis of a specific cancer predisposition syndrome. Some changes do not cause the gene to function improperly and are called benign or likely benign and may help rule out a specific syndrome. Sometimes, the consequences of the change in DNA sequence are not known, and the change is called a variant of unknown significance (VUS). A VUS can be challenging to understand, but the doctor or genetic counselor can work with a patient to determine if it impacts their care.

Deciding about testing. Genetic testing for cancer predispositions is a complex process. People thinking about testing should take time to consider the benefits and risks. They should discuss the process with a genetic counselor before testing is done. If they choose testing, they should review the test results with a doctor or genetic counselor to be sure they understand the meaning of the results.

Sometimes children or adults with cancer predispositions can feel sad, anxious, or angry. Parents who pass on cancer predisposition to one or more of their children can feel guilty. Some people with cancer predispositions could have trouble getting disability coverage, life insurance, or long-term care insurance in some states. More information about genetic discrimination can be found at www.ginahelp.org.

Adapted from educational materials developed by the St. Jude Children’s Research Hospital Cancer Predisposition Program