Genetic Gastric Cancer Risk Syndromes.
Genetic Gastric Cancer Risk Syndromes.
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DOI：
10.1007/s11938-020-00312-z
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Llor X
中科院分区：
文献类型：
--
作者：
Lerner BA;Llor X
胃癌是世界上癌症死亡的主要原因之一。1%至3%的病例与特定的遗传癌症风险综合征有关。本文的目的是回顾最新的见解，以及知识的差距，关于一些最常见的遗传性胃癌综合征：遗传性弥漫性胃癌（HDGC），胃腺癌和胃近端息肉病（GAPPS），林奇综合征，腺瘤性息肉病综合征和错构瘤性息肉病综合征。携带CDH 1致病性变异但不符合HDGC临床标准的患者，由于多基因组检测而越来越多地被识别出来;他们在以前的分析中的缺失高估了胃癌的发病率。GAPPS是最近描述的与APC基因启动子1B区特异性点突变相关的遗传性胃癌综合征。CDH 1致病性变异携带者胃癌风险最高，男性和女性的累积发病率分别约为40%和30%。与Lynch综合征和腺瘤性息肉病综合征相关的突变赋予东亚人群胃癌最大的风险。GAPPS和错构瘤性息肉病综合征的胃癌风险由于其罕见性而难以估计，但突变状态可能决定风险。未来的研究需要更精确地确定这些综合征中胃癌的风险，因此可以优化筛查和预防性胃切除术的策略。
Gastric cancer is a leading cause of cancer death in the world. Between 1% and 3% of cases are associated with specific genetic cancer risk syndromes. The purpose of this article is to review the latest insights, as well as gaps in knowledge, regarding some of the most common hereditary gastric cancer syndromes: hereditary diffuse gastric cancer (HDGC), gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), Lynch syndrome, the adenomatous polyposis syndromes, and the hamartomatous polyposis syndromes. Patients carrying pathogenic variants in CDH1, but not meeting clinical criteria for HDGC, are increasingly being identified thanks to multigene panel testing; their absence from previous analyses overestimated gastric cancer penetrance. GAPPS is a recently described hereditary gastric cancer syndrome associated with specific point mutations in the promoter 1B region of the APC gene. Risk of gastric cancer is highest among carriers of pathogenic variants in CDH1, with cumulative incidences approximately 40% and 30% for men and women, respectively. Mutations associated with Lynch syndrome and adenomatous polyposis syndromes confer greatest risk for gastric cancer in East Asian populations. Risk of gastric cancer in GAPPS and hamartomatous polyposis syndromes is difficult to estimate due to their rarity, but mutation status likely determines risk. Future research is needed to more precisely define risk of gastric cancer in these syndromes, so strategies for screening and prophylactic gastrectomy can be optimized.