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Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

2014; Nature Portfolio; Volume: 46; Issue: 9 Linguagem: Inglês

10.1038/ng.3064

1546-1718

Chen Wu, Zhaoming Wang, Xin Song, Xiaoshan Feng, Christian C. Abnet, Jie He, Nan Hu, Xianbo Zuo, Wen Tan, Qimin Zhan, Zhibin Hu, Zhonghu He, Wei‐Hua Jia, Yifeng Zhou, Kai Yu, Xiao‐Ou Shu, Jian‐Min Yuan, Wei Zheng, Xueke Zhao, Shegan Gao, Zhiqing Yuan, Fuyou Zhou, Zong-Min Fan, Jili Cui, Hongli Lin, Xue-Na Han, Bei Li, Xi Chen, Sanford M. Dawsey, Linda M. Liao, Maxwell P. Lee, Ti Ding, You‐Lin Qiao, Zhihua Liu, Yu Liu, Dianke Yu, Jiang Chang, Lixuan Wei, Yu‐Tang Gao, Woon‐Puay Koh, Yong‐Bing Xiang, Ze‐Zhong Tang, Jin‐Hu Fan, Jingjing Han, Shengli Zhou, Peng Zhang, Dongyun Zhang, Yuan Yuan, Ying Huang, Chunling Liu, Kan Zhai, Yan Qiao, Guangfu Jin, Chuanhai Guo, Jian-Hua Fu, Xiaoping Miao, Changdong Lu, Haijun Yang, Chaoyu Wang, William A. Wheeler, Mitchell H. Gail, Meredith Yeager, Jeff Yuenger, Er-Tao Guo, Aili Li, Wei Zhang, Xuemin Li, Liangdan Sun, MA Bao-gen, Yan Li, Sa Tang, Xiu-Qing Peng, Jing Liu, Amy Hutchinson, Kevin B. Jacobs, Carol Giffen, Laurie Burdette, Joseph F. Fraumeni, Hongbing Shen, Ke Yang, Yi‐Xin Zeng, Tangchun Wu, Peter Kraft, Charles C. Chung, Margaret A. Tucker, Zhichao Hou, Yali Liu, Yanlong Hu, Yu Liu, Li Wang, Yuan Guo, Li-Sha Chen, Xiao Liu, Teng Ma, Hui Meng, Li Sun, Xinmin Li, Xiumin Li, Jian-Wei Ku, Yingfa Zhou, Liu-Qin Yang, Zhou Wang, Yin Li, Qirenwang Qige, Wen-jun Yang, Guangyan Lei, Longqi Chen, En‐Min Li, Ling Yuan, Wenbin Yue, Ran Wang, Lu-Wen Wang, Xueping Fan, Fang-Heng Zhu, Weixing Zhao, Yimin Mao, Mei Zhang, Guo-Lan Xing, Jilin Li, Min Soo Han, Jingli Ren, Bin Liu, Shu‐Wei Ren, Qing‐Peng Kong, Feng Li, Ilyar Sheyhidin, Wei Wu, Yanrui Zhang, Feng Changwei, Jin Wang, Yu-Hua Yang, Hong-Zhang Hao, Qi-De Bao, Baochi Liu, Aiqun Wu, Dong Xie, Wancai Yang, Liang Wang, Xiao-Hang Zhao, Shuqing Chen, Jun‐Yan Hong, Xuejun Zhang, Neal D. Freedman, Alisa M. Goldstein, Dongxin Lin, Philip R. Taylor, Lidong Wang, Stephen J. Chanock,

Cancer-related gene regulation

Dongxin Lin, Philip Taylor, Li-Dong Wang and colleagues have now pooled three genome-wide association analyses of esophageal squamous cell carcinoma, finding two new risk loci at genome-wide significance and an HLA class II locus of significance in high-risk populations. They reanalyze the strength of evidence for previously published risk loci. We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS)1,2,3 of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82–0.88; P = 7.72 × 10−20) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85–0.91; P = 3.10 × 10−13). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22–1.46; P = 1.99 × 10−10). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.