Editor’s Note: I am so thrilled that my colleague and friend, Jennifer Propst, is able to share her genetic cancer expertise with all of us through this piece. It can be complicated to understand the genetic testing process related to cancer and this piece does a beautiful job of explaining things. Please leave a comment about your thoughts on this piece, and perhaps future topics you’d like addressed as well. We are listening! – DJL
When a cancer diagnosis hits close to home, there are many questions. How serious is it? What is the prognosis? What is the best treatment? Why did it happen? The answers to those questions and many more about cancer diagnosis, treatment, and prevention now include genetics and genetic testing.
Knowing whether or not there is a risk for cancer running in a family is important to help define future cancer risk and medical management for cancer patients and their loved ones. However, only about 5% to 10% of cancer risk is inherited through a family. The rest of cancer occurs due to spontaneous mistakes or mutations in the genes that tell the cells how to work. As a result, the cells grow and act in an abnormal way and may develop into tumors and cancer. This is why all cancer is considered to be genetic.
Even though all cancer is genetic, it does not always run in families.
All cancers do involve genetic mutations or variants that change gene functioning, but they aren’t always inherited. For example, tumor cells originally had the same genetic profile as the person they grew in. However, as the tumor cells grow and change, gene errors or mutations occur. These errors or mutations can be acquired over someone’s lifetime spontaneously or by carcinogens such as ultraviolet rays of the sun or tobacco smoke. Early genetic changes causing cancer are usually in genes that promote cell division leading to uncontrolled cell growth or genes responsible for repairing the DNA code. After the initial gene changes, many more mistakes occur that lead to things such as blood vessel formation and cell function. For more information about the genetic errors in cancer, click here.
Sometimes, the first genetic mutation or variant found in a tumor is being passed down through a family and is found in the egg or sperm cells. This is known as a hereditary predisposition to cancer and accounts for approximately 5-10% of all cancers. In this case, the increased chance or predisposition to develop a specific kind of cancer is passed down from one or both parents. It doesn’t mean an individual who inherits these gene change will develop cancer, but it does significantly increase the risk.
Understanding hereditary cancer risk
Cancer caused by an inherited predisposition is more often seen at a younger age (less than 50 years old). Patients are more likely to have bilateral cancers if the risk is to a paired body part (like breasts) and there is usually a family history of cancer. The types of cancers seen in a family with an inherited predisposition are dependent on the gene that has the mutation. There are more than 80 genes that are currently known to be associated with hereditary cancer risk. For example, inherited mutations in the BRCA1 and BRCA2 genes increase the risk for breast, ovarian, prostatic, and pancreatic cancers while MSH2 gene mutations are associated with Lynch syndrome or an increased risk to develop colon, endometrial, stomach, ovarian and other cancers.
It’s important to know that inheriting one genetic predisposition mutation does NOT guarantee the person will get cancer. Instead, it means they have an increased risk to develop cancer. Even with the same mutation in the family, not everyone with a mutation will develop cancer or even the same types of cancers. The inheritance pattern and the chance to pass on the mutation(s) will depend on the gene involved.
What are the genetic tests for cancer?
There are two main types of genetic tests that can help us to understand cancer in an individual a little better: Somatic and hereditary predisposition genetic testing. The specific test ordered will depend if the genetic testing is seeking information on the cancer tumor, a possible inherited cancer risk, or both.
Somatic genetic testing
Also known as “tumor DNA sequencing” or “tumor DNA profiling”. This form of testing is done to learn more information about the genetic mutations in the tumor that make the cancer cells grow and divide. Tumor DNA profiling can help determine if there is a targeted treatment, like a specific medication or chemotherapy agent that might be more effective in treating that specific cancer or whether patient would be eligible for a clinical trial studying a new treatment option.
In late 2017, the FDA approved two commercial tumor DNA sequencing profiling tests to aid in diagnosis and treatment decisions. Both the number of laboratories doing the testing and the types of genetic tests on tumors have continued to expand since that time.
Hereditary cancer predisposition testing
This form of testing is done when a healthcare provider would like to determine if there is a hereditary cancer predisposition in the family. Testing examines the genes a person is born with, rather that the tumor. This test can look for inherited mutations or variants on few genes or via a large panel focused on many different causes for specific type of cancer(s). The best person in a family to test for a hereditary cancer predisposition is someone who has developed cancer. This individual’s result will be the most informative if a mutation is found. Before doing hereditary cancer predisposition testing, it is recommended that a patient see a genetic counselor to discuss the chance of a hereditary cancer predisposition. This opens a dialogue to weigh the pros and cons of genetic testing, coordinate testing, and understand the returned results.
If a specific cancer predisposition mutation(s) is found in a family, then the patient’s genetic counselor can help to plan how to discuss this finding with their family. The counselor will also help identify who is at risk to have inherited the change based on family history. In this case targeted testing looking just for that family specific gene mutation or mutations is all that is needed to determine who inherited it and who did not.
Boiling the genetics of cancer down
It can be very surprising for people to learn that all cancer is genetic, but some of that shock may fade away as they learn about the differences between the genetics of a tumor and the genetics of a person. Genetic testing on both a person and their tumor can open the window to explore the impact on the family and the treatment plan for a patient’s cancer.
About Jennifer Propst, MS, LCGC. Jennifer is a licensed genetic counselor who graduated from Indiana University in 2004. She worked with both pediatric and adult patients in a variety of areas including general genetics, perinatal, cancer, and chronic disease. At Emory Genetics she served as a clinical research coordinator specializing in lysosomal storage diseases.
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