Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, 201 Section 2, Shih-Pai Road, Taipei 11217, Taiwan.
Biomed Res Int. 2013;2013:396272. doi: 10.1155/2013/396272. Epub 2013 Mar 5.
Mismatch repair (MMR) and germline E-cadherin (CDH1) mutations are two of the major pathways of carcinogenesis in familial gastric cancer (GC). A total of 260 sporadic and 66 familial GC patients were enrolled and molecular and survival differences were compared. Familial GC patients had earlier onset and were diagnosed at an earlier stage and had both a better 5-year overall survival rate and 3-year disease-free survival rate compared with sporadic GC patients. Only in diffuse type GC, the MSI-H phenotype and abnormal MMR protein expression were significantly higher in familial GC than in sporadic GC. In MSI-H GC, MLH1 promoter methylation was slightly higher in sporadic GC than familial GC (50% versus 23.1%), while the frequency of MMR gene mutation was slightly higher in familial GC than in sporadic GC (15.4% versus 3.1%). All of the patients with MMR gene mutation had diffuse type GC. Among familial GC patients with CDH1 mutation, most patients (72.3%) had diffuse type GC. In summary, for familial GC patients, we recommend screening of MSI status and CDH1 mutation especially for diffuse type GC. Because of the low incidence, mutation analysis of MMR gene might be considered in MSI-H familial GC with diffuse type only.
错配修复（MMR）和胚系 E-钙黏蛋白（CDH1）突变是家族性胃癌（GC）发生的两个主要途径。共纳入 260 例散发性和 66 例家族性 GC 患者，比较了分子和生存差异。家族性 GC 患者发病更早，诊断更早，与散发性 GC 患者相比，5 年总生存率和 3 年无病生存率均更高。仅在弥漫型 GC 中，家族性 GC 的 MSI-H 表型和异常 MMR 蛋白表达明显高于散发性 GC。在 MSI-H GC 中，散发性 GC 的 MLH1 启动子甲基化略高于家族性 GC（50%比 23.1%），而家族性 GC 的 MMR 基因突变频率略高于散发性 GC（15.4%比 3.1%）。所有 MMR 基因突变的患者均为弥漫型 GC。在 CDH1 突变的家族性 GC 患者中，大多数患者（72.3%）为弥漫型 GC。总之，对于家族性 GC 患者，我们建议筛查 MSI 状态和 CDH1 突变，特别是弥漫型 GC。由于发病率低，仅在 MSI-H 家族性弥漫型 GC 中才考虑 MMR 基因突变分析。
