Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Pathology, Peking University Shenzhen Hospital, Shenzhen, China.
Int J Cancer. 2020 Jun 1;146(11):3077-3086. doi: 10.1002/ijc.32914. Epub 2020 Feb 25.
Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) predisposition syndrome. We performed a large-scale study to assess a screening strategy for identifying LS in Chinese CRC patients in routine clinical testing. A total of 4,195 eligible CRCs were universally screened. Then, 8.7% of CRCs were detected with dMMR. The incidence of LS was 2.7% (115 of 4,195) in this cohort; among patients over 70 years of age, only 0.3% (2 of 678) were diagnosed as LS. Then, 17.4% of LS cases showed large genomic deletions/duplications. LS probands developed CRCs predominantly at proximal colon location. The frequency of BRAF V600E mutation among Chinese CRCs was significantly lower than that among Western populations, and MLH1 promoter methylation significantly improved the efficiency of genetic screening for LS among MLH1-deficient patients. A comprehensive molecular testing strategy that includes detection of large genomic rearrangements is imperative for the diagnosis of LS. Among CRC patients aged 70 years or younger, a selective strategy for LS screening might be considered for routine clinical testing.
林奇综合征（LS）是最常见的遗传性结直肠癌（CRC）易患综合征。我们进行了一项大规模研究，以评估在常规临床检测中识别中国 CRC 患者 LS 的筛查策略。对总共 4195 例合格的 CRC 进行了普遍筛查。然后，检测到 8.7%的 CRC 存在 dMMR。在该队列中，LS 的发病率为 2.7%（4195 例中有 115 例）；在 70 岁以上的患者中，只有 0.3%（678 例中有 2 例）被诊断为 LS。然后，17.4%的 LS 病例显示出较大的基因组缺失/重复。LS 先证者主要在近端结肠部位发生 CRC。中国 CRC 中 BRAF V600E 突变的频率明显低于西方人群，而 MLH1 启动子甲基化显著提高了 MLH1 缺陷患者 LS 遗传筛查的效率。对于 LS 的诊断，包括检测大基因组重排的综合分子检测策略是必不可少的。在 70 岁或以下的 CRC 患者中，对于 LS 筛查，可以考虑在常规临床检测中采用有选择性的策略。
