Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Section of Gastroenterology, San Diego Veterans Affairs Healthcare System, San Diego, CA, USA.
Aliment Pharmacol Ther. 2022 Apr;55(8):960-977. doi: 10.1111/apt.16826. Epub 2022 Mar 21.
Lynch syndrome (LS) is an autosomal dominant familial condition caused by a pathogenic variant (PV) in a DNA mismatch repair gene, which then predisposes carriers to various cancers.
To review the pathogenesis, clinical presentation, differential diagnosis and clinical strategies for detection and management of LS.
A narrative review synthesising knowledge from published literature, as well as current National Comprehensive Cancer Network guidelines for management of LS was conducted.
LS tumours are characterised by unique pathogenesis, ultimately resulting in hypermutation, microsatellite instability and high immunogenicity that has significant implications for cancer risk, clinical presentation, treatment and surveillance. LS is one of the most common hereditary causes of cancer, and about 1 in 279 individuals carry a PV in an LS gene that predisposes to associated cancers. Individuals with LS have increased risks for colorectal, endometrial and other cancers, with significant variation in lifetime risk by LS-associated gene.
As genetic testing becomes more widespread, the number of individuals identified with LS is expected to increase in the population. Understanding the pathogenesis of LS informs current strategies for detection and clinical management, and also guides future areas for clinical innovation. Unravelling the mechanisms by which these tumours evolve may help to more precisely tailor management by the gene involved.
林奇综合征（LS）是一种常染色体显性遗传疾病，由 DNA 错配修复基因中的致病性变异（PV）引起，使携带者易患多种癌症。
综述 LS 的发病机制、临床表现、鉴别诊断以及检测和管理的临床策略。
对已发表文献中的知识以及目前国家综合癌症网络（National Comprehensive Cancer Network）LS 管理指南进行综合叙述性综述。
LS 肿瘤的发病机制独特，最终导致高突变率、微卫星不稳定性和高免疫原性，这对癌症风险、临床表现、治疗和监测有重要影响。LS 是最常见的遗传性癌症病因之一，约每 279 个人中就有 1 人携带易患相关癌症的 LS 基因中的 PV。LS 患者患结直肠癌、子宫内膜癌和其他癌症的风险增加，LS 相关基因的终生风险存在显著差异。
随着基因检测的普及，预计人群中 LS 患者的数量将会增加。对 LS 发病机制的了解为目前的检测和临床管理策略提供了信息，并指导未来的临床创新领域。揭示这些肿瘤演变的机制可能有助于更精确地根据相关基因来定制管理。
