Decourtye-Espiard Lyvianne, Godwin Tanis, Guilford Parry
Cancer Genetics Laboratory, Te Aho Matatū, Department of Biochemistry, Otākou Whakaihu Waka, University of Otago, Dunedin (Otepoti), New Zealand (Aotearoa).
J R Soc N Z. 2025 Jun 16;55(6):2636-2651. doi: 10.1080/03036758.2025.2511007. eCollection 2025.
Hereditary Diffuse Gastric Cancer (HDGC) is a high risk cancer syndrome caused predominantly by germline mutations in the gene. HDGC is characterised by a lifetime risk of advanced diffuse-type gastric (stomach) cancer of up to 70%, and an additional 40% lifetime risk of lobular breast cancer in women. Since the first description of HDGC in three whānau Māori in 1998, our understanding of this syndrome's life history and clinical behaviour has steadily evolved, leading to changes to its clinical management. In particular, it is now evident that the signet ring cell carcinomas that develop in the stomachs of pathogenic variant carriers have an indolent phase, although the factors that drive progression of these early cancers to advanced disease remain to be identified. This indolent phase provides the opportunity for chemoprevention to be considered as an alternative to prophylactic surgery as a risk reduction strategy. Here, we describe the evolution of our knowledge of HDGC, with particular reference to the syndrome's penetrance, tumour spectrum and pathology.
遗传性弥漫性胃癌（HDGC）是一种主要由该基因种系突变引起的高风险癌症综合征。HDGC的特征是终生患晚期弥漫型胃癌（胃癌）的风险高达70%，女性患小叶乳腺癌的终生风险额外增加40%。自1998年首次在三个毛利家族中描述HDGC以来，我们对该综合征的生命历程和临床行为的理解不断发展，导致其临床管理发生了变化。特别是，现在很明显，致病性变异携带者胃中发生的印戒细胞癌有一个惰性阶段，尽管驱动这些早期癌症进展为晚期疾病的因素仍有待确定。这个惰性阶段为将化学预防作为降低风险策略替代预防性手术提供了机会。在此，我们描述了我们对HDGC认识的演变，特别提及该综合征的外显率、肿瘤谱和病理学。
