From the Guidelines
Lynch syndrome is a genetic condition that significantly increases the risk of colorectal, endometrial, and other cancers, and individuals with a family history of these cancers should undergo genetic testing and regular screening to reduce their risk of developing cancer. The condition is caused by mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2, or EPCAM) and follows an autosomal dominant inheritance pattern, meaning children of affected individuals have a 50% chance of inheriting the condition 1. According to the American Gastroenterological Association Institute guideline, patients with Lynch syndrome have an estimated lifetime cumulative incidence of colorectal cancer up to 80% and endometrial cancer up to 60% 1.
Key Points
- Lynch syndrome increases the risk of colorectal, endometrial, ovarian, stomach, small intestine, urinary tract, and other cancers
- Genetic testing is recommended for individuals with a family history of these cancers, especially at young ages
- Management includes regular colonoscopies starting at age 20-25 (every 1-2 years), endometrial screening for women, and consideration of preventive surgeries like hysterectomy after childbearing
- Some patients may benefit from aspirin for cancer prevention, as it has been shown to reduce the risk of colorectal cancer in individuals with Lynch syndrome 1
Screening and Prevention
The National Comprehensive Cancer Network (NCCN) recommends screening all patients with colorectal cancer for Lynch syndrome and provides recommendations for surveillance for early detection and prevention of Lynch syndrome-associated cancers 1. Regular colonoscopies and endometrial screening are crucial for early detection and prevention of cancer in individuals with Lynch syndrome. Additionally, consideration of preventive surgeries like hysterectomy after childbearing may be beneficial for some patients.
Family Genetic Counseling
Lynch syndrome follows an autosomal dominant inheritance pattern, meaning children of affected individuals have a 50% chance of inheriting the condition, making family genetic counseling important 1. Family genetic counseling is essential to identify individuals at risk and provide them with appropriate screening and prevention strategies. By prioritizing genetic testing, regular screening, and preventive measures, individuals with Lynch syndrome can reduce their risk of developing cancer and improve their overall quality of life.
From the Research
Definition and Characteristics of Lynch Syndrome
- Lynch syndrome (LS) is an inherited predisposition to colorectal cancer (CRC), responsible for 3-5% of all CRC 2.
- It is characterized by the early occurrence of colorectal neoplastic lesions, with variable incidences depending on the type of pathogenic variants in MMR genes (MLH1, MSH2, MSH6, PMS2 and EPCAM) and demographics factors such as gender, body mass index, tobacco use and physical activity 2.
- Individuals with Lynch syndrome have a 50%-70% lifetime risk of colorectal cancer, 40%-60% risk of endometrial cancer, and increased risks of several other malignancies 3.
Screening and Surveillance
- Colorectal screening by colonoscopy is efficient because it is associated with a reduction >50% of both CRC incidence and CRC related mortality 2.
- Most guidelines recommend high definition screening colonoscopies in dedicated centers, starting at the age of 20-25 years old, with a surveillance interval of 1-2 years 2.
- Regular screening for Lynch syndrome reduces CRC-related mortality; however, high CRC incidence during regular colonoscopy screening suggests the possibility of nonpolypoid carcinogenesis 4.
- Screening for endometrial cancer has been recommended, but no benefits have been shown in recent studies 5.
Diagnosis and Testing
- Lynch syndrome is caused by germline mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2 3.
- In a subset of patients, Lynch syndrome is caused by 3' end deletions of the EPCAM gene, which can lead to epigenetic silencing of the closely linked MSH2 3.
- Microsatellite instability testing and/or immunohistochemical testing can be used to identify tumor mismatch repair deficiencies 3.
- Universal screening of all newly diagnosed endometrial cancers is recommended, as a significant number of LS-associated endometrial carcinomas are missed using clinical, histologic, and locational screening parameters 6.