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

• DOI: 10.1038/ng.3064
• Publication Date: 2014-08-17T20:17:37Z
• Authors: Chen Wu; Zhaoming Wang; Xin Song; Xiao-Shan Feng; Christian C Abnet; Jie He; Nan Hu; Xian-Bo Zuo; Wen Tan; Qimin Zhan; Zhibin Hu; Zhonghu He; Weihua Jia; Yifeng Zhou; Kai Yu; Xiao-Ou Shu; Jian-Min Yuan; Wei Zheng; Xue-Ke Zhao; She-Gan Gao; Zhi-Qing Yuan; Fu-You Zhou; Zong-Min Fan; Ji-Li Cui; Hong-Li Lin; Xue-Na Han; Bei Li; Xi Chen; Sanford M Dawsey; Linda 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; Jing-Jing Han; Sheng-Li Zhou; Peng Zhang; Dong-Yun Zhang; Yuan Yuan; Ying Huang; Chunling Liu; Kan Zhai; Yan Qiao; Guangfu Jin; Chuanhai Guo; Jianhua Fu; Xiaoping Miao; Changdong Lu; Haijun Yang; Chaoyu Wang; William A Wheeler; Mitchell Gail; Meredith Yeager; Jeff Yuenger; Er-Tao Guo; Ai-Li Li; Wei Zhang; Xue-Min Li; Liang-Dan Sun; Bao-Gen Ma; Yan Li; Sa Tang; Xiu-Qing Peng; Jing Liu; Amy Hutchinson; Kevin Jacobs; Carol Giffen; Laurie Burdette; Joseph F Fraumeni; Hongbing Shen; Yang Ke; Yixin Zeng; Tangchun Wu; Peter Kraft; Charles C Chung; Margaret A Tucker; Zhi-Chao Hou; Ya-Li Liu; Yan-Long Hu; Yu Liu; Li Wang; Guo Yuan; Li-Sha Chen; Xiao Liu; Teng Ma; Hui Meng; Li Sun; Xin-Min Li; Xiu-Min Li; Jian-Wei Ku; Ying-Fa Zhou; Liu-Qin Yang; Zhou Wang; Yin Li; Qirenwang Qige; Wen-Jun Yang; Guang-Yan Lei; Long-Qi Chen; En-Min Li; Ling Yuan; Wen-Bin Yue; Ran Wang; Lu-Wen Wang; Xue-Ping Fan; Fang-Heng Zhu; Wei-Xing Zhao; Yi-Min Mao; Mei Zhang; Guo-Lan Xing; Ji-Lin Li; Min Han; Jing-Li Ren; Bin Liu; Shu-Wei Ren; Qing-Peng Kong; Feng Li; Ilyar Sheyhidin; Wu Wei; Yan-Rui Zhang; Chang-Wei Feng; Jin Wang; Yu-Hua Yang; Hong-Zhang Hao; Qi-De Bao; Bao-Chi Liu; Ai-Qun Wu; Dong Xie; Wan-Cai Yang; Liang Wang; Xiao-Hang Zhao; Shu-Qing Chen; Jun-Yan Hong; Xue-Jun Zhang; Neal D Freedman; Alisa M Goldstein; Dongxin Lin; Philip R Taylor; Li-Dong Wang; Stephen J Chanock
• Keywords: Male; Risk; 0301 basic medicine; Esophageal Neoplasms; Genotype; 610; Middle Aged; Polymorphism, Single Nucleotide; Article; 3. Good health; 03 medical and health sciences; Asian People; Genetic Loci; Case-Control Studies; Carcinoma, Squamous Cell; Humans; Female; Genetic Predisposition to Disease; Esophageal Squamous Cell Carcinoma; Alleles; Genome-Wide Association Study

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 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.