Background and Aims: Lynch syndrome (LS) is currently one of the most prevalent hereditary cancer conditions, accounting for 3% of all colorectal cancers and for up to 15% of those with DNA mismatch repair (MMR) deficiency, and it was one of the first historically identified. The understanding of the molecular carcinogenesis of LS tumors has progressed significantly in recent years. We aim to review the most recent advances in LS research and explore genotype-based approaches in surveillance, personalized cancer prevention, and treatment strategies. Methods: PubMed was searched to identify relevant studies, conducted up to December 2023, investigating molecular carcinogenesis in LS, surveillance strategies, cancer prevention, and treatment in LS tumors. Results: Multigene panel sequencing is becoming the benchmark in the diagnosis of LS, allowing for the detection of a pathogenic constitutional variant in one of the MMR genes. Emerging data from randomized controlled trials suggest possible preventive roles of resistant starch and/or aspirin in LS. Vaccination with immunogenic frameshift peptides appears to be a promising approach for both the treatment and prevention of LS-associated cancers, as evidenced by pre-clinical and preliminary phase 1/2a studies. Conclusions: Although robust diagnostic algorithms, including prompt testing of tumor tissue for MMR defects and referral for genetic counselling, currently exist for suspected LS in CRC patients, the indications for LS screening in cancer-free individuals still need to be refined and standardized. Investigation into additional genetic and non-genetic factors that may explain residual rates of interval cancers, even in properly screened populations, would allow for more tailored preventive strategies.
背景与目的：林奇综合征是目前最常见的遗传性癌症综合征之一，占所有结直肠癌病例的3%，在DNA错配修复缺陷病例中占比高达15%，也是历史上最早被识别的遗传性癌症综合征之一。近年来，对林奇综合征肿瘤分子致癌机制的认识取得了显著进展。本文旨在综述林奇综合征研究的最新进展，并探讨基于基因型的监测策略、个体化癌症预防及治疗方案。方法：通过检索PubMed数据库，收集截至2023年12月关于林奇综合征分子致癌机制、监测策略、癌症预防及治疗的相关研究。结果：多基因panel测序正逐渐成为林奇综合征诊断的金标准，能够检测出错配修复基因中的致病性胚系变异。随机对照试验的新数据显示，抗性淀粉和/或阿司匹林可能对林奇综合征具有预防作用。临床前及初步1/2a期研究表明，免疫原性移码肽疫苗接种在预防和治疗林奇综合征相关癌症方面展现出良好前景。结论：尽管目前针对结直肠癌患者疑似林奇综合征已建立完善的诊断流程（包括及时进行肿瘤组织错配修复缺陷检测及遗传咨询转诊），但对未患癌个体的林奇综合征筛查指征仍需进一步细化和标准化。即使在规范筛查人群中，仍需探究可能导致间期癌残留率的其他遗传及非遗传因素，以制定更具针对性的预防策略。
Lynch Syndrome: From Multidisciplinary Management to Precision Prevention
肿瘤(癌症)患者之家