Understanding Lynch Syndrome and Associated Cancer Risk: Future Preventive Considerations

In this sixth episode of OncChats: Understanding Lynch Syndrome and Cancer Risk, of Columbia University Herbert Irving Comprehensive Cancer Center, Fay Kastrinos, MD, MPH, shares future considerations for optimizing the identification of Lynch syndrome and other efforts underway to prevent colorectal cancer in those who have this condition.

It’s fair to say that many advances have been made related to Lynch syndrome. Future considerations also involve immunoprevention in Lynch syndrome, as well as the consideration of germline genetic testing in all colon cancers—even in the general population—specifically to optimize the identification of Lynch syndrome.

Immunoprevention may be an option for the prevention of microsatellite instability–related colon cancer. Lynch syndrome represents an ideal condition for the development of a preventive cancer vaccine. The mutations induced by mismatch repair deficiency are predictable, and therefore, can result in a defined set of neoantigens. As such, Lynch syndrome carriers may be able to potentially benefit from a cancer prevention vaccine.

Current studies are underway [to further explore] the prevention of CRC in patients with Lynch syndrome, in addition to those who have survived colon cancer or those who have metastatic disease.

Germline genetic testing should be considered in all colon cancer cases; this would not miss any Lynch syndrome carrier. Since institutions vary currently in what type of tumor testing is performed, germline testing for all colon cancers would seem foolproof. Germline testing can always be paired with any tumor testing that is conducted and this approach can also provide equitable care which would extend to historically marginalized populations, many of whom do not have regular access to genetic evaluation.

Identifying all Lynch syndrome carriers with colon cancer allows us to also target the at-risk family members, which is done through cascade testing. When the identified familial gene variant is detected in the patients [with colon cancer], we have the opportunity to test the at-risk relatives, many of whom do not have cancer. If they’re identified [to have] Lynch syndrome, we can then pursue screening and prevention strategies; these are our “pre-vivors” that we aim to keep cancer free.

Lastly, I want you to consider population-based testing for Lynch syndrome. The Office of Public Health Genomics of the Centers of Disease Control and Prevention have currently identified Lynch syndrome, as well as hereditary breast and ovarian cancer syndrome, as tier 1 conditions that are eligible for population-based genetic testing in the future. This is because testing for these conditions has significant potential for positive impact on public health based on all the [accumulated] evidence and the guideline recommendations to reduce cancer risk and mortality. In the future, we may very well be testing for Lynch syndrome in healthy young adults, even in the absence of family cancer history.

In summary, many advances have been made for the identification, management, and the treatment of Lynch syndrome. Additional work will continue to optimize cancer prevention and potential cure for Lynch syndrome. Thank you.