Lynch Syndrome Research Advances Cancer Prevention and Vaccine Trials
Research into Lynch syndrome is advancing cancer prevention through aspirin therapy, vaccine trials, and a major North American study examining why some patients develop cancer while others remain protected.
New research into Lynch syndrome — a genetic mutation that can increase the risk of several cancers, including colorectal cancer — is leading to treatments and clinical trials that can help people with the diagnosis reduce their cancer risk.
Lynch syndrome is the most common inherited genetic predisposition to colorectal cancer. About 10% of all colon cancer patients have some genetic or hereditary predisposition that drove them to develop that cancer, and Lynch syndrome is the most common of these genetic syndromes.
Strategies to reduce cancer risk in Lynch syndrome patients include encouraging people to avoid cancer-causing habits like smoking and excessive drinking and scheduling them for colonoscopies at an early age and higher frequency. Prescribing aspirin has been found to reduce the long-term risk of colon cancer by 50% in patients with Lynch syndrome. The landmark study had patients on aspirin for two years, and starting at five years, their risk of colon cancer began to decrease. Following those patients out to 20 years, their risk was reduced by 50%. In the general population, patients have to take aspirin for at least five years, but they don't see a benefit until 20 years down the line. Because aspirin has short-term risks including stomach ulcers and thinning of the blood, it is not recommended as a cancer prevention method in the general population.
Because Lynch syndrome tumor cells tend to exhibit abnormal proteins, they are often able to be treated with targeted therapy that is aimed at those proteins, boosting a patient's immune system to help destroy them. Because those proteins are also found in precancerous cells in patients with Lynch syndrome, researchers are now testing the efficacy of a vaccine shot for people with Lynch syndrome that targets suspect cells before they have the opportunity to become cancerous.
The CU Anschutz Cancer Center is part of a phase II trial to test a vaccine in Lynch syndrome patients. The center completed accrual in 2025, and is now in the follow-up phase. In this phase, researchers will follow patients for two years to see if they develop any colorectal polyps following the vaccine. The study is randomized so that some patients receive a placebo.
As researchers learn more about Lynch syndrome and how to detect the genetic changes that cause it, they are discovering that not everyone with Lynch syndrome develops cancer. The University of Colorado is leading a North American effort to prospectively observe individuals with Lynch syndrome to understand their long-term outcomes.
Known as the Lynch syndrome INtegrative Epidemiology And GEnetics (LINEAGE) consortium and taking place at 35 sites in the U.S. and Canada, the study looks at factors including how patients were diagnosed, their medical risk factors and other medical conditions, including immunocompromised and immunosuppressed patients, and lifestyle information such as stress levels and habits. Researchers will also take tissue samples and blood samples to start to develop biological signatures of risk.