Genetic Disorder Reference Sheet: Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer)

May 28, 2024 by Suzanne M. Mahon DNS, RN, AOCN®, AGN-BC, FAAN

Lynch syndrome, now referred to as hereditary nonpolyposis colorectal cancer (HNPCC), was first identified ( in a family in 1895. In 1966, Henry Lynch discovered ( a series of families with colon and other cancers in Nebraska. Today, the evidence demonstrates that HNPCC is associated with germline pathogenic variants in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes, which are mismatch repair (MMR) genes.

MMR genes encode MMR proteins that repair DNA defects during replication; alterations in the genes result in neoplasm formation. Deficient mismatch repair (dMMR) is associated with high levels of microsatellite instability (MSI-H) and suggests potential responsiveness to anti-programmed cell death 1 (PD-1)–based immune checkpoint inhibitor immunotherapy, which makes it a predictive biomarker (

Cancer Risks

MMR genes are susceptibility biomarkers ( because germline detection of a pathogenic variant in one of the genes may indicate potential risks for the patient and potentially other family members. Malignancy risk varies with the gene (see sidebar), but an estimated annual 4,300 colorectal and 1,800 endometrial cancer diagnoses are attributed ( to HNPCC.

According to the National Comprehensive Cancer Network’s ( (NCCN’s) Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Colorectal (version 2.2023), risk for female breast cancer may also be increased but the magnitude is unclear. Individuals with HNPCC are also at risk for nonmalignant skin conditions, including sebaceous adenocarcinomas, sebaceous adenomas, and keratoacanthomas.

Indications for Germline Testing

Per the NCCN guidelines, individuals with any of the following should be referred for genetic counseling:

Management and Recommendations for Care

Individuals with a known pathogenic variant associated with HNPCC need lifelong cancer screening, but the recommendations are complex and constantly evolving. Regularly reviewing their screening plan with a genetics professional ensures they are current and appropriate. Testing is typically offered ( around age 20–25 so that intensive screening can begin in that timeframe.

The NCCN guidelines and other recommendations ( for care factor the specific gene with the pathogenic variant and its associated risks, as well as the individual’s personal and family history, and may include:

Nursing Implications

Patients and families with HNPCC need ongoing support and education to ensure that the extensive screening guidelines are followed. As children in these families approach the age of 20–25, they should be offered the option of testing to clarify risk and whether they would benefit from more intensive screening. Supportive educational messages should reiterate that early detection of cancers is possible with appropriate screening and that risk-reducing measures will help in cancer prevention, ultimately decreasing the morbidity and mortality associated with an HNPCC diagnosis.

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