Lynch syndrome (LS) is an autosomal dominant disorder characterized by increased risks of colorectal and endometrial cancers. LS is defined by pathogenic variants in mismatch repair (MMR) genes, including MLH1, MSH2, and MSH6. Data on the prevalence and associated cancer risks of LS in the Han Chinese population remain limited. In this study, using a broad biobank approach through the Taiwan Precision Medicine Initiative (TPMI), we identified LS-associated MMR gene variants within a cohort of 42,828 participants from a Taiwanese medical center. A total of 89 individuals were found to carry pathogenic MMR variants: MLH1 (n = 22, 25%), MSH2 (n = 47, 53%), and MSH6 (n = 20, 22%). The overall prevalence of MMR variants was calculated, and cancer incidence rates among carriers were determined. The prevalence of MMR variants in the study population was 1 in 481. The distribution of MLH1, MSH2, and MSH6 variants were 24.7%, 52.8%, and 22.5%, respectively. Cumulative cancer incidence rates of carriers were 40.9% for MLH1 carriers, 29.8% for MSH2, and 40% for MSH6. Among the 19 individuals who underwent colonoscopy screening, the prevalence of polyps was similar to that of the control group (adenoma detection rate: 32% vs 26%,p= 0.585). A meticulous analysis of the detected polyps in seven participants, considering factors such as location, size, morphology, and pathological features, showed no significant differences from controls. A significant cancer risk is associated with LS-related MMR variants in the Taiwanese population. The apparent under diagnosis of LS highlights the urgent need for enhanced surveillance and genetic counseling in this demographic. Our findings suggest that adjustments in the current screening protocols may be warranted to better identify and manage at-risk individuals.
林奇综合征（LS）是一种常染色体显性遗传病，其特征是结直肠癌和子宫内膜癌的发病风险显著增高。该病由错配修复（MMR）基因的致病性变异所定义，相关基因包括MLH1、MSH2和MSH6。目前关于汉族人群中LS的患病率及相关癌症风险的数据仍较为有限。本研究通过台湾精准医疗计划（TPMI）采用广泛的生物样本库方法，在一家台湾医疗中心的42,828名参与者队列中，识别了与LS相关的MMR基因变异。共发现89名个体携带致病性MMR变异：MLH1（22例，占25%）、MSH2（47例，占53%）和MSH6（20例，占22%）。研究计算了MMR变异的总体患病率，并确定了携带者的癌症发病率。研究人群中MMR变异的患病率为1/481。MLH1、MSH2和MSH6变异的分布比例分别为24.7%、52.8%和22.5%。携带者的累积癌症发病率分别为：MLH1携带者40.9%，MSH2携带者29.8%，MSH6携带者40%。在接受结肠镜筛查的19名个体中，息肉的检出率与对照组相似（腺瘤检出率：32% vs 26%，p=0.585）。对其中7名参与者检出的息肉进行细致分析，综合考虑位置、大小、形态和病理特征等因素，结果显示与对照组无显著差异。在台湾人群中，LS相关的MMR变异与显著的癌症风险相关。LS诊断明显不足的现状凸显了在该人群中加强监测和遗传咨询的迫切需求。我们的研究结果表明，可能需要对当前的筛查方案进行调整，以更好地识别和管理高危个体。
肿瘤(癌症)患者之家