Oliveira Carla, Suriano Gianpaolo, Ferreira Paulo, Canedo Paulo, Kaurah Pardeep, Mateus Rita, Ferreira Ana, Ferreira António C, Oliveira Maria José, Figueiredo Céu, Carneiro Fátima, Keller Gisela, Huntsman David, Machado José Carlos, Seruca Raquel
Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto, Portugal.
Hered Cancer Clin Pract. 2004 May 15;2(2):51-64. doi: 10.1186/1897-4287-2-2-51.
Approximately 10% of gastric cancer cases show familial clustering but only 1-3% of gastric carcinomas arise as a result of inherited gastric cancer predisposition syndromes. Direct proof that Hereditary Gastric Cancer a genetic disease with a germline gene defect has come from the demonstration of co-segregation of germline E-cadherin (CDH1) mutations with early onset diffuse gastric cancer in families with an autosomal dominant pattern of inheritance (HDGC). E-cadherin is a transmembrane calcium-dependent cell-adhesion molecule involved in cell-junction formation and the maintenance of epithelial integrity. In this review, we describe frequency and type of CDH1 mutations in sporadic and familial gastric cancer. Further we demonstrate the functional significance of some CDH1 germline missense mutations found in HDGC. We also discuss the CDH1 polymorphisms that have been associated to gastric cancer. We report other types of malignancies associated to HDGC, besides diffuse gastric cancer. Moreover, we review the data available on putative alternative candidate genes screened in familial gastric cancer. Finally, we briefly discuss the role of low-penetrance genes and Helicobacter pylori in gastric cancer. This knowledge is a fundamental step towards accurate genetic counselling, in which a highly specialised pre-symptomatic therapeutic intervention should be offered.
大约10%的胃癌病例呈现家族聚集性，但只有1%-3%的胃癌是由遗传性胃癌易感综合征引起的。遗传性胃癌是一种具有种系基因缺陷的遗传性疾病，其直接证据来自于在具有常染色体显性遗传模式（HDGC）的家族中，种系E-钙黏蛋白（CDH1）突变与早发性弥漫性胃癌的共分离现象。E-钙黏蛋白是一种跨膜钙依赖性细胞黏附分子，参与细胞连接的形成和上皮完整性的维持。在这篇综述中，我们描述了散发性和家族性胃癌中CDH1突变的频率和类型。此外，我们还展示了在HDGC中发现的一些CDH1种系错义突变的功能意义。我们还讨论了与胃癌相关的CDH1多态性。我们报告了除弥漫性胃癌外，与HDGC相关的其他类型恶性肿瘤。此外，我们回顾了在家族性胃癌中筛选出的假定替代候选基因的现有数据。最后，我们简要讨论了低 penetrance 基因和幽门螺杆菌在胃癌中的作用。这些知识是迈向准确遗传咨询的重要一步，在遗传咨询中应提供高度专业化的症状前治疗干预。
