Epigenetics Laboratory, Basic Research Division, Instituto Nacional de Cancerología (INCAN), México.
Hereditary Cancer Clinic, Clinical Research Division, Instituto Nacional de Cancerología (INCAN), México.
Clin Res Hepatol Gastroenterol. 2022 Apr;46(4):101820. doi: 10.1016/j.clinre.2021.101820. Epub 2021 Oct 14.
It is estimated that up to 10% of gastric carcinomas show familial aggregation. In contrast, around 1-3 % (approximately 33,000 yearly) are genuinely hereditary. Hereditary diffuse gastric cancer (HDGC) is a rare malignancy characterized by autosomal dominant inheritance of pathological variants of the CDH1 and CTNNA1 genes encoding the adhesion molecules E-cadherin and α-catenin, respectively. The multifocal nature of the disease and the difficulty of visualizing precursor lesions by endoscopy underscore the need to be aware of this malignancy as surgical prevention can be fully protective. Here, we provide an overview of the main epidemiological, clinical, genetic, and pathological features of HDGC, as well as updated guidelines for its diagnosis, genetic testing, counseling, surveillance, and management. We conclude that HDGC is a rare, highly penetrant disease that is difficult to diagnose and manage, so it is necessary to correctly identify it to offer patients and their families' adequate management following the recommendations of the IGCL. A critical point is identifying a mutation in HDGC families to determine whether unaffected relatives are at risk for cancer.
据估计，高达 10%的胃癌表现出家族聚集性。相比之下，约有 1-3%（约 33,000 例/年）是真正遗传性的。遗传性弥漫性胃癌（HDGC）是一种罕见的恶性肿瘤，其特征是病理变异的 CDH1 和 CTNNA1 基因分别编码黏附分子 E-钙黏蛋白和α-连环蛋白的常染色体显性遗传。该疾病的多灶性性质和内窥镜下难以观察到前驱病变，突显了需要意识到这种恶性肿瘤，因为手术预防可以完全保护。在这里，我们提供了 HDGC 的主要流行病学、临床、遗传和病理特征的概述，以及其诊断、基因检测、咨询、监测和管理的最新指南。我们的结论是，HDGC 是一种罕见的、高外显率的疾病，难以诊断和管理，因此有必要正确识别它，以便根据 IGCL 的建议为患者及其家属提供适当的管理。一个关键点是在 HDGC 家族中识别出突变，以确定是否有未受影响的亲属有患癌症的风险。
