Wu Chen, Wang Zhaoming, Song Xin, Feng Xiao-Shan, Abnet Christian C, He Jie, Hu Nan, Zuo Xian-Bo, Tan Wen, Zhan Qimin, Hu Zhibin, He Zhonghu, Jia Weihua, Zhou Yifeng, Yu Kai, Shu Xiao-Ou, Yuan Jian-Min, Zheng Wei, Zhao Xue-Ke, Gao She-Gan, Yuan Zhi-Qing, Zhou Fu-You, Fan Zong-Min, Cui Ji-Li, Lin Hong-Li, Han Xue-Na, Li Bei, Chen Xi, Dawsey Sanford M, Liao Linda, Lee Maxwell P, Ding Ti, Qiao You-Lin, Liu Zhihua, Liu Yu, Yu Dianke, Chang Jiang, Wei Lixuan, Gao Yu-Tang, Koh Woon-Puay, Xiang Yong-Bing, Tang Ze-Zhong, Fan Jin-Hu, Han Jing-Jing, Zhou Sheng-Li, Zhang Peng, Zhang Dong-Yun, Yuan Yuan, Huang Ying, Liu Chunling, Zhai Kan, Qiao Yan, Jin Guangfu, Guo Chuanhai, Fu Jianhua, Miao Xiaoping, Lu Changdong, Yang Haijun, Wang Chaoyu, Wheeler William A, Gail Mitchell, Yeager Meredith, Yuenger Jeff, Guo Er-Tao, Li Ai-Li, Zhang Wei, Li Xue-Min, Sun Liang-Dan, Ma Bao-Gen, Li Yan, Tang Sa, Peng Xiu-Qing, Liu Jing, Hutchinson Amy, Jacobs Kevin, Giffen Carol, Burdette Laurie, Fraumeni Joseph F, Shen Hongbing, Ke Yang, Zeng Yixin, Wu Tangchun, Kraft Peter, Chung Charles C, Tucker Margaret A, Hou Zhi-Chao, Liu Ya-Li, Hu Yan-Long, Liu Yu, Wang Li, Yuan Guo, Chen Li-Sha, Liu Xiao, Ma Teng, Meng Hui, Sun Li, Li Xin-Min, Li Xiu-Min, Ku Jian-Wei, Zhou Ying-Fa, Yang Liu-Qin, Wang Zhou, Li Yin, Qige Qirenwang, Yang Wen-Jun, Lei Guang-Yan, Chen Long-Qi, Li En-Min, Yuan Ling, Yue Wen-Bin, Wang Ran, Wang Lu-Wen, Fan Xue-Ping, Zhu Fang-Heng, Zhao Wei-Xing, Mao Yi-Min, Zhang Mei, Xing Guo-Lan, Li Ji-Lin, Han Min, Ren Jing-Li, Liu Bin, Ren Shu-Wei, Kong Qing-Peng, Li Feng, Sheyhidin Ilyar, Wei Wu, Zhang Yan-Rui, Feng Chang-Wei, Wang Jin, Yang Yu-Hua, Hao Hong-Zhang, Bao Qi-De, Liu Bao-Chi, Wu Ai-Qun, Xie Dong, Yang Wan-Cai, Wang Liang, Zhao Xiao-Hang, Chen Shu-Qing, Hong Jun-Yan, Zhang Xue-Jun, Freedman Neal D, Goldstein Alisa M, Lin Dongxin, Taylor Philip R, Wang Li-Dong, Chanock Stephen J
State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health, Bethesda, Maryland, USA.
Nat Genet. 2014 Sep;46(9):1001-1006. doi: 10.1038/ng.3064. Epub 2014 Aug 17.
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.
我们对三项针对中国汉族人群食管鳞状细胞癌（ESCC）的全基因组关联研究（GWAS）进行了联合（汇总）分析（5337例ESCC病例和5787例对照），并对9654例ESCC病例和10058例对照进行了随访。在调整了年龄、性别、研究及两个特征向量的逻辑回归模型中，两个新位点达到全基因组显著性水平，分别为5q31.2处的rs7447927（等位基因比数比（OR）=0.85，95%置信区间（CI）=0.82 - 0.88；P = 7.72×10⁻²⁰）和17p13.1处的rs1642764（等位基因OR = 0.88，95% CI = 0.85 - 0.91；P = 3.10×10⁻¹³）。rs7447927是TMEM173中的同义单核苷酸多态性（SNP），rs1642764是ATP1B2中靠近TP53的内含子SNP。此外，6p21.32处HLA II类区域的一个位点（rs35597309）在ESCC风险最高的两个人群中达到全基因组显著性水平（OR = 1.33，95% CI = 1.22 - 1.46；P = 1.99×10⁻¹⁰）。我们的联合分析总体上鉴定出了新的ESCC易感位点，以及太行山地区ESCC高风险人群特有的一个新位点。
