Defined lifestyle and germline factors predispose Asian populations to gastric cancer
Defined lifestyle and germline factors predispose Asian populations to gastric cancer
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DOI：
10.1126/sciadv.aav9778
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发表时间：
2020-05-01
期刊：
影响因子：
13.6
通讯作者：
Aburatani, Hiroyuki
中科院分区：
文献类型：
--
作者：
Suzuki, Akihiro;Katoh, Hiroto;Aburatani, Hiroyuki
种系和环境对胃癌（GC）发展的影响及其种族差异目前还知之甚少。在这里，我们对 531 名 GC（319 名亚洲人和 212 名非亚洲人）进行了基因组规模的跨种族分析。有一个独特的 GC 亚类具有明显的酒精相关突变特征和强烈的亚洲特异性，几乎所有这些都可归因于饮酒行为、吸烟习惯和亚洲特有的 ALDH2 等位基因缺陷。酒精相关的 GC 具有低突变负荷和特征性免疫学特征。此外，我们在日本GC中发现了频繁的（7.4%）种系CDH1变异，其中大部分归因于日本人和韩国人共有的一些重复出现的单核苷酸变异，这表明东亚人中存在共同的祖先事件。具体来说，大约五分之一的弥漫型 GC 可归因于酒精摄入和 ALDH2 等位基因缺陷或 CDH1 变异的组合。这些结果揭示了高发地区种系变异和生活方式的非典型影响。
Germline and environmental effects on the development of gastric cancers (GC) and their ethnic differences have been poorly understood. Here, we performed genomic-scale trans-ethnic analysis of 531 GCs (319 Asian and 212 non-Asians). There was one distinct GC subclass with clear alcohol-associated mutation signature and strong Asian specificity, almost all of which were attributable to alcohol intake behavior, smoking habit, and Asian-specific defective ALDH2 allele. Alcohol-related GCs have low mutation burden and characteristic immunological profiles. In addition, we found frequent (7.4%) germline CDH1 variants among Japanese GCs, most of which were attributed to a few recurrent single-nucleotide variants shared by Japanese and Koreans, suggesting the existence of common ancestral events among East Asians. Specifically, approximately one-fifth of diffuse-type GCs were attributable to the combination of alcohol intake and defective ALDH2 allele or to CDH1 variants. These results revealed uncharacterized impacts of germline variants and lifestyles in the high incidence areas.