Lynchszindróma

Lynchszindróma, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is a hereditary cancer predisposition syndrome caused by germline pathogenic variants in DNA mismatch repair genes. The most commonly affected genes are MLH1, MSH2, MSH6, and PMS2, while deletions affecting EPCAM can silence MSH2. The condition is inherited in an autosomal dominant manner with high penetrance and variable expressivity.

Loss of mismatch repair function leads to microsatellite instability (MSI) in tumors and loss of the corresponding MMR protein on immunohistochemistry. People with Lynchszindróma have an increased lifetime risk of colorectal cancer and a broad spectrum of extracolonic cancers, most notably endometrial and ovarian cancers; other associated cancers include stomach, small intestine, hepatobiliary tract, urinary tract, pancreas, brain, and skin tumors (sebaceous neoplasms in the Muir-Torre variant).

Clinical criteria used to identify families for testing include Amsterdam II criteria and the Bethesda guidelines; definitive diagnosis is established by germline genetic testing after appropriate counseling. Once a pathogenic variant is identified, cascade testing of relatives is recommended to determine who carries the mutation.

Management focuses on enhanced surveillance and risk-reducing strategies. Colonoscopy every 1–2 years starting at age 20–25 is advised. For women, discussion of endometrial assessment and potential risk-reducing gynecologic surgery after childbearing is common. In some settings, gastric or other organ surveillance may be considered based on regional risk. Evidence from trials has shown that low-dose aspirin may reduce cancer incidence with long-term use in Lynch syndrome. Relatives should be offered predictive testing to enable early detection and intervention.