{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T06:31:07Z","timestamp":1764052267550,"version":"3.45.0"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant genetic syndrome characterized by distinct clinical and genetic features. It exhibits low clinical incidence, familial clustering, early onset, insidious progression, and challenges in early diagnosis. In addition, HDGC is marked by poor tumor differentiation, high malignancy, specific gene mutations, frequent occurrence of extra-gastric tumors, and a high risk of inheritance, which poses significant challenges to clinical medicine, medical genetics, and reproductive medicine. In this study, we have reported a case of HDGC in a three-generation Chinese family of four individuals. By integrating clinical, pathological, imaging, genetic mutation, family history, diagnostic and treatment process, and the survival outcome data, it fully demonstrates the clinical heterogeneity of HDGC and the considerable dilemmas encountered in its management. These findings together provide valuable insights into the clinical diagnosis and treatment of related cases, literature research, as well as the management of cancer-related genetic diseases and reproductive health.<\/jats:p>","DOI":"10.3389\/fonc.2025.1634470","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T06:27:29Z","timestamp":1764052049000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hereditary diffuse gastric cancer: a case report"],"prefix":"10.3389","volume":"15","author":[{"given":"Lili","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youzhi","family":"An","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanjun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"B1","unstructured":"World Cancer Report: Cancer Research for Cancer Prevention[EB\/OL]\n          \n          2020"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.16662\/j.cnki.1674-0742.2022.04.194","article-title":"Progress in diagnosis and treatment of hereditary gastric cancer","volume":"41","author":"Li","year":"2022","journal-title":"Chin Foreign Med J"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.12354\/j.issn.1000-8179.2021.20211801","article-title":"Expert consensus on clinical diagnosis and treatment of familial hereditary tumors in China (2021 edition) (3)-familial hereditary gastric cancer","volume":"48","author":"Xie","year":"2021","journal-title":"Clin Oncol China"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30219-9","article-title":"Hereditary diffuse gastric cancer: updated clinical practice guidelines","volume":"21","author":"Vanessa","year":"2020","journal-title":"Lancet Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1186\/s12884-023-05772-6","article-title":"Prenatal diagnosis of hereditary diffuse gastric cancer: a case report","volume":"23","author":"Xiao","year":"2023","journal-title":"BMC Pregnancy Childbirth"},{"key":"B6","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13046-023-02622-3","article-title":"Current advances in understanding the molecular profile of hereditary diffuse gastric cancer and its clinical implications","volume":"42","author":"Lim","year":"2023","journal-title":"J Exp Clin Cancer Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-051019-103216","article-title":"Hereditary diffuse gastric cancer: approaches to screening, surveillance, and treatment","volume":"72","author":"Nastazja","year":"2021","journal-title":"Annu Rev Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/bjsopen\/zrad023","article-title":"Hereditary colorectal, gastric, and pancreatic cancer:comprehensive review","volume":"7","author":"Sepp\u00e4l\u00e4","year":"2023","journal-title":"BJS Open"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1159\/000505664","article-title":"Pathogenic germline mutations in Chinese patients with gastric cancer identified by next-generation sequencing","volume":"98","author":"Zhou","year":"2020","journal-title":"Oncology"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2020.6155","article-title":"Hereditary diffuse gastric cancer syndrome and the role of CDH1","volume":"156","author":"Gamble","year":"2021","journal-title":"JAMA Surg"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s11938-020-00312-z","article-title":"Genetic gastric Cancer risk syndromes","volume":"18","author":"Lerner","year":"2020","journal-title":"Curr Treat Options Gastroenterol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1177\/1758835920967238","article-title":"Hereditary diffuse gastric cancer therapeutic roadmap: current and novel approaches in a nutshell","volume":"12","author":"Rami","year":"2020","journal-title":"Ther Adv Med Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.10754","article-title":"Outcomes after prophylactic gastrectomy for hereditary diffuse gastric cancer","volume":"105","author":"van der Kaaij","year":"2018","journal-title":"Br J Surg"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.asjsur.2019.10.007","article-title":"Impact of postoperative complications on long-term outcomes of patients following surgery for gastric cancer: a systematic review and meta-analysis of 64 follow-up studies","volume":"43","author":"Li","year":"2020","journal-title":"Asian J Surg"},{"key":"B15","doi-asserted-by":"publisher","first-page":"25","DOI":"10.21037\/cco-23-36","article-title":"CDH1 and hereditary diffuse gastric cancer: a narrative review","volume":"12","author":"Gregory","year":"2023","journal-title":"Chin Clin Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-017-9976-y","article-title":"High-risk individuals\u2019 perceptions of reproductive genetic testing for CDH1 mutations","volume":"16","author":"Hallowell","year":"2017","journal-title":"Familial Cancer"},{"key":"B17","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s13053-022-00239-9","article-title":"Attitudes toward preimplantation genetic testing and quality of life among individuals with hereditary diffuse gastric cancer syndrome","volume":"20","author":"Shah","year":"2022","journal-title":"Hered Cancer Clin Pract"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14030728","article-title":"Surgery for hereditary diffuse gastric cancer: long-term outcomes","volume":"14","author":"Forrester","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3969\/ji.ssn.1671-7171.2025.02.005","article-title":"Pathological features of primary TP53-mutant gastric cancer and factors influencing patient prognosis[J","volume":"42","author":"Ji","year":"2025","journal-title":"J Clin Res"},{"key":"B20","volume-title":"Effect of Neuregulin 1 (NRG1) on Invasion, Metastasis, and Molecular Mechanisms in Esophageal Squamous Cell Carcinoma [D]","author":"Yang","year":"2022"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e10406","DOI":"10.7759\/cureus.10406","article-title":"Significance of E-cadherin gene mutations in patients with hereditary diffuse gastric cancer syndrome: A systematic review","volume":"12","author":"Goud","year":"2020","journal-title":"Cureus"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e2245836","DOI":"10.1001\/jamanetworkopen.2022.45836","article-title":"Whole-exome sequencing among chinese patients with hereditary diffuse gastric cancer","volume":"5","author":"Liu","year":"2022","journal-title":"JAMA Netw Open"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12123726","article-title":"Hereditary diffuse gastric cancer: A comparative cohort study according to pathogenic variant status","volume":"12","author":"Marwitz","year":"2020","journal-title":"Cancers (Basel)"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1634470\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T06:27:38Z","timestamp":1764052058000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1634470\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":23,"alternative-id":["10.3389\/fonc.2025.1634470"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1634470","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,25]]},"article-number":"1634470"}}