Introduction: Surveillance of Lynch syndrome (LS) is recommended to reduce cancer-risk. There is an increased awareness that cancer-risk may vary with mismatch-repair mutation and family history. However, gene-specific and family-specific surveillance are not recommended. Therefore, we aimed to estimate the cumulative incidence of lesions and to assess the cancer-risk by family history and mismatch-repair mutation (MMR).

Methods: Single-centre retrospective cohort of all individuals (n = 241) in a specialized institution was conducted.

Results: Forty-eight percent of individuals inherited MSH2 mutations, 32% MLH1, 15% MSH6 and 5% PMS2. The calculated cumulative incidence for any cancer increased with age. By age 70, the cumulative incidence for low-risk, high-risk adenomas and CRC was estimated at 66.6%, 57.7% and 25.7%, respectively. By age 70, the cumulative incidence of endometrial cancer (EC), gastric cancer and urinary tract cancer was estimated at 17.3%, 3.3% and 12.6%, respectively. MLH1 and MSH2 mutation carriers had lower mean age of CRC diagnosis than MSH6 and PMS2 [MLH1:44(CI95% 38–50); MSH2:43(CI95% 40–47); MSH6:52(CI95% 45–59); PMS2:46(CI95% 35–57)]. The risk of EC was higher when family history was present (RR = 2.39, CI95%[1.3;4.6]). MSH6 mutation carriers had higher risk of EC comparative to other MMR mutation carriers (RR = 1.9, p = .09). The risk of urinary tract cancer was higher with MSH2 (RR = 8.4, CI95%[2.7;25.9]) and positive family history (RR = 10.8, CI95%[1.4;82.8]).

Conclusion: This cohort demonstrates the effectiveness of LS surveillance and suggests possible tailored surveillance strategies by gene mutation and family history.

简介：建议进行Lynch综合征（LS）监测以降低患癌风险。人们越来越意识到，癌症风险可能因错配修复突变和家族史而异。但是，不建议进行基因特异性和家族特异性监测。因此，我们旨在通过家族史和错配修复突变（MMR）来评估病变的累积发生率并评估癌症风险。

方法： 在专门机构中对所有个体（n = 241）进行单中心回顾性队列研究。

结果： 48％的个体遗传了MSH2突变，32％的MLH1、15％的MSH6和5％的PMS2。计算出的任何癌症累积发病率都随着年龄的增长而增加。到70岁时，低风险，高风险腺瘤和CRC的累积发生率分别估计为66.6％，57.7％和25.7％。到70岁时，子宫内膜癌（EC），胃癌和尿路癌的累积发生率分别估计为17.3％，3.3％和12.6％。MLH1和MSH2突变携带者的CRC诊断平均年龄低于MSH6和PMS2 [MLH1：44（CI95％38–50）；MSH2：43（CI95％40–47）; MSH6：52（CI95％45–59）; PMS2：46（CI95％35–57）]。有家族史的患者发生EC的风险较高（RR = 2.39，CI95％[1.3; 4.6]）。与其他MMR突变携带者相比，MSH6突变携带者具有较高的EC风险（RR = 1.9，p  = .09）。MSH2（RR = 8.4，CI95％[2.7; 25.9]）和家族史阳性（RR = 10.8，CI95％[1.4; 82.8]）患尿路癌的风险更高。

结论：该队列研究证明了LS监测的有效性，并通过基因突变和家族史提出了可能的定制监测策略。