Authors
Neil A J Ryan, Richard Gallon, Terri McVeigh, Kevin J Monahan, Gabriela Moeslein, David N Church, Mev Domínguez-Valentin, Tracy Smith
Published in
Lancet (London, England). Nov 12, 2026. Epub Nov 12, 2026.
Abstract
Lynch syndrome is the most common inherited cancer predisposition syndrome, affecting approximately one in 350-450 individuals, yet the majority of carriers remain undiagnosed, representing a substantial and preventable public health burden. Caused by germline pathogenic variants in DNA mismatch repair (MMR) genes, Lynch syndrome confers markedly elevated and heterogeneous risks of colorectal, endometrial, and multiple extracolonic cancers. Advances in molecular diagnostics, particularly universal tumour testing for MMR deficiency, have transformed case identification and enabled targeted germline testing and cascade screening of relatives at risk. Despite these advances, implementation remains inconsistent, with substantial attrition across diagnostic pathways and inequities in access to care. Preventive strategies-including colonoscopic surveillance, aspirin chemoprevention, and risk-reducing surgery-are effective but require gene-specific and individualised application. Therapeutically, the immunogenic biology of MMR-deficient tumours has positioned Lynch syndrome at the forefront of precision oncology, with immune checkpoint inhibitors delivering substantial benefit and emerging vaccine strategies offering promise for cancer interception. In this Review, we provide an integrated overview of Lynch syndrome across the continuum of care, highlighting advances in biology, diagnosis, prevention, and treatment, while emphasising the crucial need to align scientific progress with equitable and effective health-system delivery.
PMID:
43020098
Bibliographic data and abstract were imported from PubMed on 13 Nov 2026.
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