Defined lifestyle and germline factors predispose Asian populations to gastric cancer

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2020-05-06 DOI:10.1126/sciadv.aav9778

Akihiro Suzuki, Hiroto Katoh, Daisuke Komura, Miwako Kakiuchi, Amane Tagashira, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Genta Nagae, Shiro Fukuda, Takayoshi Umeda, Yasushi Totoki, Hiroyuki Abe, Tetsuo Ushiku, Tetsuya Matsuura, Eiji Sakai, Takashi Ohshima, Sachiyo Nomura, Yasuyuki Seto, Tatsuhiro Shibata, Yasushi Rino, Atsushi Nakajima, Masashi Fukayama, Shumpei Ishikawa, Hiroyuki Aburatani

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引用次数: 27

Abstract

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.

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明确的生活方式和种系因素使亚洲人易患胃癌

人们对种系和环境对胃癌（GC）发病的影响及其种族差异知之甚少。在这里，我们对 531 例胃癌（319 例亚裔和 212 例非亚裔）进行了基因组规模的跨种族分析。有一个独特的GC亚类具有明确的酒精相关突变特征和强烈的亚裔特异性，几乎所有的突变都可归因于酒精摄入行为、吸烟习惯和亚裔特有的ALDH2等位基因缺陷。与酒精相关的 GCs 突变负荷低，免疫学特征明显。此外，我们还发现日本 GCs 中 CDH1 生殖系变异频繁（7.4%），其中大部分变异归因于日本人和韩国人共有的几个重复出现的单核苷酸变异，这表明东亚人之间存在共同的祖先事件。具体而言，约五分之一的弥散型 GCs 可归因于酒精摄入量和 ALDH2 等位基因缺陷或 CDH1 变异。这些结果揭示了种系变异和生活方式对高发病率地区的未定性影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.