Department of Clinical Genetics, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Clinical Genetics, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
Clin Gastroenterol Hepatol. 2020 May;18(5):1112-1120.e1. doi: 10.1016/j.cgh.2019.08.043. Epub 2019 Aug 27.
BACKGROUND & AIMS: Patients with Lynch syndrome are offered the same colorectal cancer (CRC) surveillance programs (colonoscopy every 2 years), regardless of the pathogenic DNA mismatch repair gene variant the patient carries. We aimed to assess the yield of surveillance for patients with these variants in MLH1, MSH2, MSH6, and PMS2.
We analyzed data on colonoscopy surveillance, including histopathology analysis, from all patients diagnosed with Lynch syndrome (n = 264) at a single center. We compared the development of (advanced) adenomas and CRC among patients with pathogenic variants in the DNA mismatch repair genes MLH1 (n = 55), MSH2 (n = 44), MSH6 (n = 143), or PMS2 (n = 22) over 1836 years of follow-up (median follow-up of 6 years per patient).
At first colonoscopy, CRC was found in 8 patients. During 916 follow-up colonoscopies, CRC was found in 9 patients. No CRC was found in patients with variants in MSH6 or PMS2 over the entire follow-up period. There were no significant differences in the number of colonoscopies with adenomas or advanced adenomas among the groups. The median time of adenoma development was 3 years (IQR, 2-6 years). There were no significant differences in time to development of adenoma. However, patients with variants in MSH6 had a significant longer time to development of advanced neoplasia (advanced adenoma or CRC) than patients in the other groups. Six carriers died during follow up (5 from cancer, of which 3 from pancreatic cancer).
No CRC was found during follow-up of patients with Lynch syndrome carrying pathogenic variants in MSH6; advanced neoplasia developed over shorter follow-up time periods in patients with pathogenic variants in MLH1 or MSH2. The colonoscopy interval for patients with pathogenic variants in MSH6 might be increased to 3 years from the regular 2-year interval.
携带林奇综合征相关致病性 DNA 错配修复基因突变的患者，无论其携带的具体基因变异为何，均接受相同的结直肠癌（CRC）监测方案（每 2 年进行一次结肠镜检查）。我们旨在评估 MLH1、MSH2、MSH6 和 PMS2 中这些变异患者的监测结果。
我们分析了一家单中心所有被诊断为林奇综合征（n=264）患者的结肠镜监测数据，包括组织病理学分析。我们比较了 MLH1（n=55）、MSH2（n=44）、MSH6（n=143）或 PMS2（n=22）中致病性错配修复基因突变患者在 1836 年的随访期间（每位患者的中位随访时间为 6 年）中（高级）腺瘤和 CRC 的发展情况。
首次结肠镜检查时发现 8 例 CRC。916 次随访结肠镜检查中，发现 9 例 CRC。在整个随访期间，MSH6 或 PMS2 变异患者均未发现 CRC。各组间腺瘤或高级腺瘤结肠镜检查的数量无显著差异。腺瘤发生的中位时间为 3 年（IQR，2-6 年）。腺瘤发展时间无显著差异。然而，与其他组相比，MSH6 变异患者发生高级肿瘤的时间明显延长（高级腺瘤或 CRC）。6 名携带者在随访期间死亡（5 例死于癌症，其中 3 例死于胰腺癌）。
在携带 MSH6 致病性变异的林奇综合征患者的随访中未发现 CRC；与 MLH1 或 MSH2 致病性变异患者相比，MSH6 致病性变异患者的高级肿瘤发生在更短的随访时间内。MSH6 致病性变异患者的结肠镜检查间隔可从常规的 2 年延长至 3 年。
