Background/Objectives: Gastric cancer (GC) remains a leading cause of cancer mortality worldwide. While most cases are sporadic, approximately 10% show familial clustering with only a minority explained by known hereditary syndromes. The remaining, termed familial non-hereditary gastric cancer (FNHGC), lack a defined high-penetrance germline mutation. This review aims to summarize current knowledge regarding the diagnosis, risk factors, molecular characteristics and management of FNHGC. Methods: A comprehensive narrative review of the literature was conducted focusing on epidemiologic, molecular and clinical studies addressing families with multiple GC cases but no identified germline mutation. Results: The etiology of FNHGC is multifactorial, andH. pylori, with its related chronic gastritis, is probably the key driver. Familial clustering likely occurs when combined with other elements such as genetic polymorphisms, shared exposures to risk factors or even epigenetic phenomena. Molecular profiling reveals distinct patterns in familial tumors such as more frequent microsatellite instability; somaticCDH1promoter hypermethylation; and recurrent somatic mutations inTP53, RHOA and DNA repair genes. Current management focuses on genetic testing to rule out hereditary syndromes, endoscopic surveillance and mitigation of risk factors, with eradication ofH. pyloriparamount. Conclusions: FNHGC represents a distinct subgroup of GC characterized by a multifactorial etiology related to exposure to risk factors and genetic susceptibility although significant gaps remain in fully explaining the condition. Ongoing research holds promise to provide tools for better detection and prevention in order to reduce the burden of GC in familial settings.
**背景/目的：** 胃癌仍是全球癌症死亡的主要原因。虽然大多数病例为散发性，但约10%呈现家族聚集性，其中仅少数可由已知的遗传综合征解释。其余病例被称为家族性非遗传性胃癌，其缺乏明确的高外显率胚系突变。本综述旨在总结当前关于家族性非遗传性胃癌的诊断、危险因素、分子特征及管理方面的认识。 **方法：** 对文献进行了全面的叙述性综述，重点关注涉及多例胃癌但未发现胚系突变的家族的流行病学、分子及临床研究。 **结果：** 家族性非遗传性胃癌的病因是多因素的，幽门螺杆菌及其相关的慢性胃炎可能是关键驱动因素。当与其他因素（如基因多态性、共同暴露于危险因素，甚至表观遗传现象）相结合时，便可能出现家族聚集。分子谱分析揭示了家族性肿瘤的独特模式，例如更频繁的微卫星不稳定性、体细胞CDH1启动子高甲基化，以及TP53、RHOA和DNA修复基因中反复出现的体细胞突变。目前的管理重点在于通过基因检测排除遗传综合征、进行内镜监测、减轻危险因素，其中根除幽门螺杆菌至关重要。 **结论：** 家族性非遗传性胃癌代表了胃癌的一个独特亚组，其特征是与危险因素暴露和遗传易感性相关的多因素病因，尽管在完全解释该疾病方面仍存在显著空白。持续的研究有望为在家族环境中更好地检测和预防胃癌提供工具，从而减轻其负担。
肿瘤(癌症)患者之家