Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is a hereditary cancer syndrome significantly increasing the risk of colorectal cancer (CRC) and various extracolonic cancers, including endometrial, ovarian, and gastric cancers. LS results from germline pathogenic variants (GPVs) in DNA mismatch repair (MMR) genes, such asMLH1,MSH2,MSH6, andPMS2, leading to microsatellite instability (MSI). This review explores the multifaceted aspects of LS, covering clinical presentation, genetic underpinnings, and emerging therapeutic strategies. The discussion explores the importance of identifying at-risk individuals, facilitating personalized cancer surveillance and prevention strategies. Molecular insights into distinguishing between sporadic and LS-associated cancers are also examined, with a focus on somatic testing methods, including MSI and immunohistochemistry (IHC). The gynecological cancer risks, particularly those related to endometrial and ovarian malignancies, are addressed, underscoring the need for early detection and risk-reducing interventions. Recent advancements in the management of colorectal and other LS-related cancers are highlighted, with particular attention to the growing role of immunotherapy, including immune checkpoint inhibitors, and immunoprevention strategies. With ongoing advances in our understanding of LS, opportunities for earlier detection, more effective prevention, and innovative treatments continue to expand. This narrative review adopts a multidisciplinary approach to provide a comprehensive understanding of LS, from its genetic basis to current clinical and therapeutic practices, with the ultimate goal of improving patient outcomes and enhancing the quality of care.
林奇综合征（Lynch syndrome, LS），亦称遗传性非息肉病性结直肠癌（hereditary nonpolyposis colorectal cancer, HNPCC），是一种遗传性癌症综合征，可显著增加结直肠癌（colorectal cancer, CRC）及多种肠外癌症（包括子宫内膜癌、卵巢癌和胃癌）的患病风险。该病源于DNA错配修复（mismatch repair, MMR）基因（如MLH1、MSH2、MSH6和PMS2）的胚系致病性变异（germline pathogenic variants, GPVs），进而导致微卫星不稳定性（microsatellite instability, MSI）。本文综述从多维度探讨林奇综合征，涵盖其临床表现、遗传学基础及新兴治疗策略。文中重点讨论了识别高危个体的重要性，以推动个体化的癌症监测与预防策略的实施。同时，本文分析了从分子层面区分散发性癌症与林奇综合征相关癌症的方法，重点关注包括MSI检测和免疫组织化学（immunohistochemistry, IHC）在内的体细胞检测技术。文中还特别阐述了妇科癌症风险，尤其是与子宫内膜癌和卵巢癌相关的风险，强调早期发现及降低风险干预措施的必要性。此外，本文综述了结直肠癌及其他林奇综合征相关癌症管理的最新进展，特别关注免疫治疗（包括免疫检查点抑制剂）及免疫预防策略日益重要的作用。随着对林奇综合征认识的不断深入，早期发现、更有效预防及创新治疗的机会持续扩大。本综述采用多学科视角，旨在全面阐述林奇综合征——从其遗传基础到当前临床与治疗实践，最终目标在于改善患者预后并提升医疗质量。
肿瘤(癌症)患者之家