Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations

被引：265

作者：

Wu, Chen ^{[1
,2
]}

Hu, Zhibin ^{[3
]}

He, Zhonghu ^{[4
]}

Jia, Weihua ^{[5
,6
]}

Wang, Feng ^{[7
]}

Zhou, Yifeng ^{[8
]}

Liu, Zhihua ^{[1
,2
]}

Zhan, Qimin ^{[1
,2
]}

Liu, Yu ^{[1
,2
]}

Yu, Dianke ^{[1
,2
]}

Zhai, Kan ^{[1
,2
]}

Chang, Jiang ^{[1
,2
]}

Qiao, Yan ^{[1
,2
]}

Jin, Guangfu ^{[3
]}

Liu, Zhe ^{[9
]}

Shen, Yuanyuan ^{[9
]}

Guo, Chuanhai ^{[4
]}

Fu, Jianhua ^{[5
,6
]}

Miao, Xiaoping ^{[7
]}

Tan, Wen ^{[1
,2
]}

Shen, Hongbing ^{[3
]}

Ke, Yang ^{[4
]}

Zeng, Yixin ^{[5
,6
]}

Wu, Tangchun ^{[7
]}

Lin, Dongxin ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, State Key Lab Mol Oncol, Canc Inst & Hosp, Beijing 100730, Peoples R China

[2] Peking Union Med Coll, Beijing 100021, Peoples R China

[3] Nanjing Med Univ, Ctr Canc, Dept Epidemiol & Biostat, Nanjing, Peoples R China

[4] Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100871, Peoples R China

[5] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol So China, Guangzhou 510275, Guangdong, Peoples R China

[6] Sun Yat Sen Univ, Ctr Canc, Dept Expt Res, Guangzhou 510275, Guangdong, Peoples R China

[7] Huazhong Univ Sci & Technol, Key Lab Environm & Hlth, Minist Educ, Sch Publ Hlth, Wuhan 430074, Peoples R China

[8] Soochow Univ, Coll Med, Lab Canc Mol Genet, Suzhou, Peoples R China

[9] Chinese Acad Sci, Beijing Inst Genom, Beijing, Peoples R China

来源：

NATURE GENETICS | 2011年 / 43卷 / 07期

基金：

中国国家自然科学基金;

关键词：

GENETIC-VARIANTS; GASTRIC-CANCER; POLYMORPHISMS; PLCE1; LINES; RUNX1; RISK; GAIN;

D O I：

10.1038/ng.849

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Esophageal squamous-cell carcinoma (ESCC) is one of the most prevalent cancers worldwide and occurs at a relatively high frequency in China. To identify genetic susceptibility loci for ESCC, we conducted a genome-wide association study on 2,031 individuals with ESCC (cases) and 2,044 controls of Chinese descent using 666,141 autosomal SNPs. We evaluated promising associations in an additional 6,276 cases and 6,165 controls of Chinese descent from different areas of China. We identified seven susceptibility loci on chromosomes 5q11, 6p21, 10q23, 12q24 and 21q22 (ranging from P = 7.48 x 10(-12) to P = 2.44 x 10(-31)); among these loci, 5q11, 6p21 and 21q22 were newly identified. Three variants in high linkage disequilibrium on 12q24 confer their risks to ESCC in a gene-lifestyle interaction manner, with more pronounced risk enhancement seen in tobacco and alcohol users. Furthermore, the identified variants had a cumulative association with ESCC risk (P(trend) = 7.92 x 10(-56)). These findings highlight the involvement of multiple genetic loci and gene-environment interaction in the development of esophageal cancer.

引用

页码：679 / U97

页数：8

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