Consultation d'Oncogénétique, Département de Médecine Oncologique, Institut Gustave Roussy, 114 rue Edouard Vaillant, Villejuif 94805, France.
J Med Genet. 2013 Jul;50(7):486-9. doi: 10.1136/jmedgenet-2012-101472. Epub 2013 May 25.
CDH1 predisposes primarily to diffuse gastric cancer (DGC). Multiple DGC cases in a family, DGC at a young age in an individual or the combination of DGC andlobular breast cancer (LBC) in an individual or a family define the hereditary DGC syndrome (HDGC), and testing for germline CDH1 mutations is warranted in HDGC.
We report all index cases from Ile-de-France in which a germline CDH1 mutation has been identified. Out of 18 cases, 7 do not fulfil the HDGC-defining criteria. Three of them are women who presented initially with bilateral LBC below age 50, without personal or family history of DGC, and who subsequently developed symptomatic DGC.
Our series of CDH1 mutation carriers is the largest to date and demonstrates that LBC might be the first manifestation of HDGC. A personal or family history of multiple LBCs at a young age, even without DGC, should prompt CDH1 mutation screening. It is paramount to identify mutation carriers early, so that they can benefit from prophylactic gastrectomy before they develop symptomatic, highly lethal DGC. We recommend a revision of the HDGC-defining criteria and propose for consideration the name 'Hereditary Diffuse Gastric and Lobular Breast Cancer' instead of HDGC.
CDH1 主要导致弥漫性胃癌（DGC）。家族中出现多个 DGC 病例、个体中年轻时出现 DGC 或个体或家族中 DGC 和 乳腺癌（LBC）并存，定义了遗传性 DGC 综合征（HDGC），需要对 HDGC 进行种系 CDH1 突变检测。
我们报告了在法兰西岛发现种系 CDH1 突变的所有指数病例。在 18 个病例中，有 7 个不符合 HDGC 的定义标准。其中 3 名女性最初表现为双侧 LBC，年龄低于 50 岁，无 DGC 个人或家族史，随后出现有症状的 DGC。
我们的 CDH1 突变携带者系列是迄今为止最大的系列，表明 LBC 可能是 HDGC 的首发表现。年轻时期多发 LBC 的个人或家族史，即使没有 DGC，也应提示进行 CDH1 突变筛查。尽早识别突变携带者至关重要，以便在出现有症状、高度致命的 DGC 之前，他们可以受益于预防性胃切除术。我们建议修订 HDGC 的定义标准，并提议考虑使用“遗传性弥漫性胃和乳腺癌”而不是 HDGC 来命名。
