Monahan Kevin John, Hopkins Laura
Family History of Bowel Cancer Clinic, Gastroenterology Department, West Middlesex University Hospital, Chelsea and Westminster Hospitals NHS Trust, London, UK.
Recent Results Cancer Res. 2016;205:45-60. doi: 10.1007/978-3-319-29998-3_4.
A positive family history is consistently reported as a risk factor for gastric cancer (GC), but the molecular basis for the familial aggregation is largely unknown. The risk associated with having one first-degree relative (FDR) with GC is approximately 1.3-3.5 fold increased. Hereditary cancer syndromes have been relatively well characterised, but their rarity largely precludes the development of trials of surveillance. In hereditary diffuse gastric cancer (HDGC), patients have a CDH1 mutation that results in a high penetrance of GC meaning that prophylactic gastrectomy is recommended, although this treatment results in significant psychosocial issues. The management of HDGC patients includes endoscopic surveillance, surgery and histological interpretation which require a high degree of selective expertise. Much of the remaining heritable risk of GC may be accounted for by low- and intermediate-penetrant genetic factors, i.e. common and rare variants, respectively. The advent of new methods such as next-generation sequencing has revealed a number of new candidate gene loci.
家族史阳性一直被认为是胃癌（GC）的一个风险因素，但家族聚集性的分子基础在很大程度上尚不清楚。有一位患GC的一级亲属（FDR）的相关风险大约增加了1.3至3.5倍。遗传性癌症综合征已得到相对较好的表征，但其罕见性在很大程度上排除了开展监测试验的可能性。在遗传性弥漫性胃癌（HDGC）中，患者存在CDH1突变，这导致GC的高外显率，这意味着建议进行预防性胃切除术，尽管这种治疗会引发重大的心理社会问题。HDGC患者的管理包括内镜监测、手术和组织学解读，这需要高度的专业选择性。GC剩余的大部分遗传风险可能分别由低和中 penetrant 遗传因素解释，即常见和罕见变异。新一代测序等新方法的出现揭示了一些新的候选基因位点。
