There are many predisposition cancer syndromes.
Angelina Jolie and Beyonce’s father have made Hereditary Breast and Ovarian Cancer syndrome (HBOC) one of the most well-known cancer predisposition syndromes. Because of these celebrities sharing their stories, many people have been able to catch earlier cancer diagnoses or even prevent cancer formation. However, there are other cancer predispositions syndromes to be aware of as well. This post will review HBOC as well as other syndromes such as Lynch syndrome and Li-Fraumeni Syndrome.
What Is Hereditary Breast and Ovarian Cancer Syndrome?
Hereditary Breast and Ovarian Cancer syndrome (HBOC) is a condition in which a person has a higher than average chance to develop breast, ovarian, prostate, pancreatic, and skin cancer. It is caused by variants (also known as mutations) in the BRCA1 or BRCA2 genes. The role of the BRCA1 and BRCA2 genes are to suppress tumor formation. If there is a variant in the gene that causes it to no longer perform this role, then there is a higher likelihood of tumor formation and cancer.
We all have two copies of the BRCA1 and BRCA2 genes. Even if the other copy of the gene is normal and does not have a variant, it may not be enough to ward off cancer. Therefore, people with variants in the BRCA1 or BRCA2 genes have increased cancer surveillance and possibly even prophylactic surgery. Prophylactic surgery is the removal of the organs that have the increased risk of cancer development. HBOC is a lifetime condition that requires attention. It is also a condition that can be passed onto someone’s children. Each time a person with HBOC has a child, there is a 50% chance that they pass on the condition. Their siblings and parents may also be also have the condition as well.
There is genetic testing available to test the person’s BRCA1 and BRCA2 genes to identify if there is a harmful variant present. Once someone receives this diagnosis, they are cared for by a healthcare provider to manage the syndrome.
What are Other Examples of Cancer Predisposition Syndromes?
A common colon cancer related syndrome is called Lynch syndrome. Lynch syndrome is caused by a harmful variant in one of 5 genes. The genes are named: MLH1, MSH2, MSH6, or PMS2 or EPCAM. When someone has Lynch syndrome, they are at an increased risk to have various cancers, primarily colorectal, endometrial, gastric, and ovarian cancer. Check out: Lynch Cancers for more information and support on the condition.
Li-Fraumeni syndrome is another cancer syndrome caused by harmful variants in the TP53 gene. The primary cancers someone is at an increased risk for are adrenocortical carcinomas, breast cancer, central nervous system tumors, osteosarcomas, and soft-tissue sarcomas. Check out: Li-Fraumeni syndrome Association for more information.
How Does Someone Know if They Have A Cancer Predisposition Syndrome?
People can learn if they have a cancer predisposition syndrome by having genetic testing of the genes that are known to be associated with a cancer predisposition syndrome. Not all cancer is because of a cancer predisposition syndrome, so there are times that people have normal genetic testing but still develop cancer. Cancer can be caused by environmental toxins and not because of an inherited harmful variant in the gene. However, if someone has had many relatives with cancer diagnoses, their relatives were young at the time of the diagnosis, and/or if they have had a cancer diagnosis at a young age or multiple diagnoses, then this increases the likelihood there is a genetic cause.
How is Genetic Testing Used to Determine if Someone Has A Cancer Predisposition Syndrome?
Genetic testing for cancer predispositions syndromes has changed throughout the years as more genes have been discovered. In the past, someone may have only been tested for a few genes. Now, numerous genes are tested in one assessment. If someone had genetic testing a few years ago, then it may be helpful to check in with their providers to see if updates or additional genes have been added for assessment.
There are few occasions where only two or three genes may be tested such as in cases where a person has an active cancer diagnosis and is deciding whether to have a bilateral mastectomy (removal of both breasts) or unilateral mastectomy/lumpectomy (removal of one breast or the area with the cancer cells). If a person has a genetic cause for their breast cancer, then there is an increased chance for them to have a recurrence, so a bilateral mastectomy may be recommended. If there is not a genetic cause identified, then person could consider only removing the breast tissue with the cancerous cells - if this was determined to be the best course of action recommended by the person’s physician.
If someone is actively being treated for a cancer diagnosis, it is critical to speak with their doctor and genetic counselor on the best approach for genetic testing.
Is Genetic Testing Always Clear?
If only - since there are new genes being discovered and limited research into the risks of having a harmful variant in those genes, there can be concerns about what to do with the information. Some cancer syndromes, like HBOC or Lynch syndrome, have clear guidelines as to how a physician should monitor for a cancer diagnosis in these individuals. However, for other cancer genes/syndromes it can be less clear how to care for those patients because of limited data.
Given the above factors, it is helpful to discuss genetic testing options with a genetic counselor to better determine what option will be the most helpful. Some people want to know about all possible cancer syndromes, so they opt to be tested for them all. Other people do not want to know about cancer syndromes that do not have clear guidelines on how to be managed, so they opt to only be screened for cancer syndromes they can actually “do something about”. Other times, people do not want to know this information at all.
Usually, the possibility of a cancer syndrome is brought up when someone has had a personal diagnosis of cancer at a younger than expected age (less than 50 years old), a rare cancer, or has had multiple family members diagnosed with cancer. This is slowly changing. People are starting to have testing proactively, before receiving a cancer diagnosis. Direct to consumer (DTC) genetic testing has helped to change the narrative.
Many articles have been written on the concerns of DTC, specifically for individuals who are trying to determine if the breast cancer in their family is genetic or not: NY Times, Huff Post, JAX . The concern is that some of the tests offered are not comprehensive and may provide false reassurance. It may even cause someone to “write off” the cancer in the family and not get properly screened.
So what should someone do if they want to determine if they have a predisposition cancer syndrome?
Oncology genetic counselors are providers that are equipped with the knowledge of adequate testing, information, and interpreting family history. Sometimes family history is the biggest determining factor of someone’s risk. There are risk models that can incorporate someone’s full clinical and family picture. Oncology genetic counselors can be found here: https://findageneticcounselor.nsgc.org/.
Resources:
https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf
https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf
* This blog constitutes general information about genetic testing and medical screening. This blog does not offer or provide medical advice or diagnosis, and nothing in this blog should be construed as medical advice or diagnosis. Do not rely on the information in this blog/article to make medical management decisions. Please consult with a medical professional before making those decisions. Do not delay in seeking professional medical advice if you think you have a medical concern. Do not disregard professional medical advice based on any information received in this blog.
