Lynch Syndrome: A Common Yet Under-Recognized Hereditary Cancer Predisposition

Lynch syndrome is the most common inherited predisposition to colorectal and endometrial (uterine) cancers, yet is it under-diagnosed. Around 90-95% of people who have Lynch syndrome are not aware of their condition. This is a major concern because many of the cancers associated with Lynch syndrome are preventable or could be detected earlier through intensive cancer surveillance. Identifying patients with Lynch syndrome also helps with testing other members of their family who may be at risk and helps ensure access to care for patients who have high risks for cancer.

Family History Risk Assessment

Identifying patients with Lynch syndrome starts with collecting a detailed family history. Patients often discuss many concerns with their primary health care provider during their visit, which means discussing family history may not always happen. If you have a personal or family history of cancer, you may want to set up a separate appointment with your health care provider to discuss your concerns. To prepare for these conversations, it is helpful to talk with family members about health issues that run in your family. It is helpful to get as many details as possible about who has had health problems, their age when the problem started, any treatment they received, whether they had any surgeries to reduce their cancer risk, and whether or not they have pursued genetic testing. If one of your relatives reaches out with these questions, please take the time to share this information, as it may help to protect the health of your entire family.  

Lynch syndrome is suspected when multiple relatives over multiple generations have had colorectal cancer or other Lynch syndrome-related cancers, or when an individual has a Lynch syndrome-related cancer at a young age (<50) or any cancer with features of Lynch syndrome.

An individual with a family history that includes some of these risk factors could benefit from meeting with a genetic counselor. The genetic counselor will fully assess the patient’s family history, discuss the potential risk for developing cancer, and determine if genetic testing would be useful.

A key benefit of determining if an individual has Lynch syndrome is helping their family members learn if they’ve also inherited this condition. To ensure that genetic testing can help the entire family, it is important for patients to share genetic test results with family members. Close relatives such as parents, siblings, and children are tested first and testing then proceeds to aunts, uncles, grandparents, nieces, nephews, and grandchildren if they are determined to be at risk. This process is called cascade testing. Genetic counselors can assist family members in pursuing testing for the known mutation in the family.

Universal Tumor Screening for Lynch Syndrome

Another way to identify patients with Lynch syndrome is through screening colorectal, endometrial, and other related cancers for Lynch syndrome at the time of diagnosis, whether there is a family history of Lynch syndrome or not. This process, called “universal tumor screening,” involves performing either a test to determine whether the tumor cells express the Lynch syndrome proteins or if the tumor has a characteristic called “microsatellite instability” which is common in Lynch syndrome. Individuals with microsatellite unstable tumors (and/or tumors that are not expressing any of the Lynch syndrome proteins) are more likely to respond to treatment with immunotherapy. Individuals with these types of tumors are also more likely to have Lynch syndrome and should be referred to a genetic counselor to discuss genetic testing. A genetic counselor can help ensure the correct genetic test(s) are performed, interpret the test results, and help patients understand how to use the information in surveillance, risk reduction, and treatment decisions.

Universal tumor screening has expanded the understanding of the cancer risks, ages of onset, and frequency of mutations for each Lynch syndrome gene. Knowing which gene is involved helps determine the age to start surveillance, the frequency of surveillance, which organs should be monitored, and informs risk reduction considerations. Lynch syndrome cancer surveillance includes earlier and more frequent colonoscopy. Many women with Lynch syndrome consider risk-reducing hysterectomy with removal of their ovaries and fallopian tubes. Surveillance for other cancers is often tailored based on the responsible gene, family history, and other risk factors.

Work has been ongoing to learn how to reduce cancer risks and perhaps prevent cancers in individuals with Lynch syndrome. There are exciting studies underway including one looking at how aspirin may best reduce the chance of developing colorectal cancer in patients with Lynch syndrome and another to develop a vaccine that may help prevent cancers in individuals with Lynch syndrome.

Looking Forward for Patients and Genetic Counselors

The National Society of Genetic Counselors (NSGC) and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer (CGA-IGC) collaborated to create a resource to help health care professionals recognize and evaluate patients with Lynch syndrome. If you suspect that you or your family may be affected by Lynch syndrome, this document can be helpful in discussing your concerns with your health care provider and getting appropriate referrals.

If health care providers and community members alike become more aware of Lynch syndrome, we can move from identifying individuals with Lynch syndrome after their cancer diagnosis to identifying healthy individuals who could take steps to help protect their health so they may never develop cancer at all.

To find a genetic counselor in your area, visit www.findageneticcounselor.com.

Joy Larsen Haidle, MS, LGC is a past-president of the National Society of Genetic Counselors and a genetic counselor at the North Memorial Health Cancer Center in Minneapolis. Heather Hampel MS, LGC is a cancer genetic counselor and Associate Director, Division of Genetics and Genetic Counseling at City of Hope.

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