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

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; Li Wang; Guo Yuan; Li Sha Chen; Xiao Liu; Teng Ma; Hui Meng; Xin 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

doi:10.1038/ng.3064

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

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 GaoZhi 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, Li Wang, Guo Yuan, Li Sha Chen, Xiao Liu, Teng Ma, Hui Meng, Xin 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

School of Medicine

Research output: Contribution to journal › Article › peer-review

103 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1001-1006
Number of pages	6
Journal	Nature genetics
Volume	46
Issue number	9
DOIs	https://doi.org/10.1038/ng.3064
State	Published - 2014

ASJC Scopus subject areas

Genetics

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10.1038/ng.3064

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Wu, C., Wang, Z., Song, X., Feng, X. S., Abnet, C. C., He, J., Hu, N., Zuo, X. B., Tan, W., Zhan, Q., Hu, Z., He, Z., Jia, W., Zhou, Y., Yu, K., Shu, X. O., Yuan, J. M., Zheng, W., Zhao, X. K., ... Chanock, S. J. (2014). Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations. Nature genetics, 46(9), 1001-1006. https://doi.org/10.1038/ng.3064

Wu, C, Wang, Z, Song, X, Feng, XS, Abnet, CC, He, J, Hu, N, Zuo, XB, Tan, W, Zhan, Q, Hu, Z, He, Z, Jia, W, Zhou, Y, Yu, K, Shu, XO, Yuan, JM, Zheng, W, Zhao, XK, Gao, SG, Yuan, ZQ, Zhou, FY, Fan, ZM, Cui, JL, Lin, HL, Han, XN, Li, B, Chen, X, Dawsey, SM, Liao, L, Lee, MP, Ding, T, Qiao, YL, Liu, Z, Liu, Y, Yu, D, Chang, J, Wei, L, Gao, YT, Koh, WP, Xiang, YB, Tang, ZZ, Fan, JH, Han, JJ, Zhou, SL, Zhang, P, Zhang, DY, Yuan, Y, Huang, Y, Liu, C, Zhai, K, Qiao, Y, Jin, G, Guo, C, Fu, J, Miao, X, Lu, C, Yang, H, Wang, C, Wheeler, WA, Gail, M, Yeager, M, Yuenger, J, Guo, ET, Li, AL, Zhang, W, Li, XM, Sun, LD, Ma, BG, Li, Y, Tang, S, Peng, XQ, Liu, J, Hutchinson, A, Jacobs, K, Giffen, C, Burdette, L, Fraumeni, JF, Shen, H, Ke, Y, Zeng, Y, Wu, T, Kraft, P, Chung, CC, Tucker, MA, Hou, ZC, Liu, YL, Hu, YL, Wang, L, Yuan, G, Chen, LS, Liu, X, Ma, T, Meng, H, Li, XM, Ku, JW, Zhou, YF, Yang, LQ, Wang, Z, Li, Y, Qige, Q, Yang, WJ, Lei, GY, Chen, LQ, Li, EM, Yuan, L, Yue, WB, Wang, R, Wang, LW, Fan, XP, Zhu, FH, Zhao, WX, Mao, YM, Zhang, M, Xing, GL, Li, JL, Han, M, Ren, JL, Liu, B, Ren, SW, Kong, QP, Li, F, Sheyhidin, I, Wei, W, Zhang, YR, Feng, CW, Wang, J, Yang, YH, Hao, HZ, Bao, QD, Liu, BC, Wu, AQ, Xie, D, Yang, WC, Wang, L, Zhao, XH, Chen, SQ, Hong, JY, Zhang, XJ, Freedman, ND, Goldstein, AM, Lin, D, Taylor, PR, Wang, LD & Chanock, SJ 2014, 'Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations', Nature genetics, vol. 46, no. 9, pp. 1001-1006. https://doi.org/10.1038/ng.3064

@article{9c2fca45d5a5415c862e0ce3ea129e22,

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

abstract = "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.",

author = "Chen Wu and Zhaoming Wang and Xin Song and Feng, {Xiao Shan} and Abnet, {Christian C.} and Jie He and Nan Hu and Zuo, {Xian Bo} and Wen Tan and Qimin Zhan and Zhibin Hu and Zhonghu He and Weihua Jia and Yifeng Zhou and Kai Yu and Shu, {Xiao Ou} and Yuan, {Jian Min} and Wei Zheng and Zhao, {Xue Ke} and Gao, {She Gan} and Yuan, {Zhi Qing} and Zhou, {Fu You} and Fan, {Zong Min} and Cui, {Ji Li} and Lin, {Hong Li} and Han, {Xue Na} and Bei Li and Xi Chen and Dawsey, {Sanford M.} and Linda Liao and Lee, {Maxwell P.} and Ti Ding and Qiao, {You Lin} and Zhihua Liu and Yu Liu and Dianke Yu and Jiang Chang and Lixuan Wei and Gao, {Yu Tang} and Koh, {Woon Puay} and Xiang, {Yong Bing} and Tang, {Ze Zhong} and Fan, {Jin Hu} and Han, {Jing Jing} and Zhou, {Sheng Li} and Peng Zhang and Zhang, {Dong Yun} and Yuan Yuan and Ying Huang and Chunling Liu and Kan Zhai and Yan Qiao and Guangfu Jin and Chuanhai Guo and Jianhua Fu and Xiaoping Miao and Changdong Lu and Haijun Yang and Chaoyu Wang and Wheeler, {William A.} and Mitchell Gail and Meredith Yeager and Jeff Yuenger and Guo, {Er Tao} and Li, {Ai Li} and Wei Zhang and Li, {Xue Min} and Sun, {Liang Dan} and Ma, {Bao Gen} and Yan Li and Sa Tang and Peng, {Xiu Qing} and Jing Liu and Amy Hutchinson and Kevin Jacobs and Carol Giffen and Laurie Burdette and Fraumeni, {Joseph F.} and Hongbing Shen and Yang Ke and Yixin Zeng and Tangchun Wu and Peter Kraft and Chung, {Charles C.} and Tucker, {Margaret A.} and Hou, {Zhi Chao} and Liu, {Ya Li} and Hu, {Yan Long} and Li Wang and Guo Yuan and Chen, {Li Sha} and Xiao Liu and Teng Ma and Hui Meng and Li, {Xin Min} and Ku, {Jian Wei} and Zhou, {Ying Fa} and Yang, {Liu Qin} and Zhou Wang and Yin Li and Qirenwang Qige and Yang, {Wen Jun} and Lei, {Guang Yan} and Chen, {Long Qi} and Li, {En Min} and Ling Yuan and Yue, {Wen Bin} and Ran Wang and Wang, {Lu Wen} and Fan, {Xue Ping} and Zhu, {Fang Heng} and Zhao, {Wei Xing} and Mao, {Yi Min} and Mei Zhang and Xing, {Guo Lan} and Li, {Ji Lin} and Min Han and Ren, {Jing Li} and Bin Liu and Ren, {Shu Wei} and Kong, {Qing Peng} and Feng Li and Ilyar Sheyhidin and Wu Wei and Zhang, {Yan Rui} and Feng, {Chang Wei} and Jin Wang and Yang, {Yu Hua} and Hao, {Hong Zhang} and Bao, {Qi De} and Liu, {Bao Chi} and Wu, {Ai Qun} and Dong Xie and Yang, {Wan Cai} and Liang Wang and Zhao, {Xiao Hang} and Chen, {Shu Qing} and Hong, {Jun Yan} and Zhang, {Xue Jun} and Freedman, {Neal D.} and Goldstein, {Alisa M.} and Dongxin Lin and Taylor, {Philip R.} and Wang, {Li Dong} and Chanock, {Stephen J.}",

note = "Funding Information: This work was funded by the National High-Tech Research and Development Program of China (2009AA022706 to D.L.), the National Basic Research Program of China (2011CB504303 to D.L. and W.T.) and the National Natural Science Foundation of China (30721001 to D.L., Q.Z. and Z.L.). We thank all the subjects and their family members whose contributions made this work possible; medical students from Zhengzhou University, Xinxiang Medical University, Zhengzhou Medical School and the Henan University of Science and Technology for sample and data collections; Q.C. Kan (The First Affiliated Hospital of Zhengzhou University) and Y. Xing (Xinxiang Medical University) for organizing field work for sample collection and finding financial support for the study; the Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, China, for genotyping; and W. Huang (Health Department of Henan Province) for field work organization. This work was supported by the Invitation Team of the Ministry of Education (2008IRTSTHN010), the National Natural Science Foundation of China (81071783), 863 High-Tech Key Projects (2012AA02A209, 2012AA02A503 and 2012AA02A201), Innovation Scientists and Technicians Troop Construction Projects of Henan Province (3047), the Key Disciplines Revitalization Plan of Zhengzhou University (20132016) and the Collaborative Innovation Center for Esophageal Cancer Research of Henan Province (20132016). The Shanghai Men{\textquoteright}s Health Study (SMHS) was supported by NCI extramural research grant R01 CA82729. The Shanghai Women{\textquoteright}s Health Study (SWHS) was supported by NCI extramural research grant R37 CA70837 and, in part, for biological sample collection, by NCI intramural research program contract NO2-CP-11010 with Vanderbilt University. The studies would not be possible without continuing support and devotion from the study participants and the staff of SMHS and SWHS. The Singapore Chinese Health Study (SCHS) was supported by NCI extramural research grants R01 CA55069, R35 CA53890, R01 CA80205 and R01 CA144034. We are indebted to the contributions of M.C. Yu and H.-P. Lee in the establishment of this cohort. The study would not be possible without the assistance in identifying cancer cases through database linkage provided by the Ministry of Health in Singapore. We are indebted to the study subjects for their continuing participation and to the staff of SCHS for their support. The Shanxi Upper Gastrointestinal Cancer Genetics Project was supported by NCI intramural research program contract NO2-SC-66211 with the Shanxi Cancer Hospital and Institute. The Nutrition Intervention Trials (NIT) was supported by NCI intramural research program contracts NO1-SC-91030 and HHSN261200477001C with the Cancer Institute and Hospital of the Chinese Academy of Medical Sciences. This research was supported in part by the intramural research program of the US NIH/NCI, the Division of Cancer Epidemiology and Genetics, and the Center for Cancer Research. This project was funded in part with federal funds from the US NIH/NCI under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US government. Publisher Copyright: {\textcopyright} 2014 Nature America, Inc. All rights reserved.",

year = "2014",

doi = "10.1038/ng.3064",

language = "English (US)",

volume = "46",

pages = "1001--1006",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "9",

}

TY - JOUR

T1 - Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

AU - Wu, Chen

AU - Wang, Zhaoming

AU - Song, Xin

AU - Feng, Xiao Shan

AU - Abnet, Christian C.

AU - He, Jie

AU - Hu, Nan

AU - Zuo, Xian Bo

AU - Tan, Wen

AU - Zhan, Qimin

AU - Hu, Zhibin

AU - He, Zhonghu

AU - Jia, Weihua

AU - Zhou, Yifeng

AU - Yu, Kai

AU - Shu, Xiao Ou

AU - Yuan, Jian Min

AU - Zheng, Wei

AU - Zhao, Xue Ke

AU - Gao, She Gan

AU - Yuan, Zhi Qing

AU - Zhou, Fu You

AU - Fan, Zong Min

AU - Cui, Ji Li

AU - Lin, Hong Li

AU - Han, Xue Na

AU - Li, Bei

AU - Chen, Xi

AU - Dawsey, Sanford M.

AU - Liao, Linda

AU - Lee, Maxwell P.

AU - Ding, Ti

AU - Qiao, You Lin

AU - Liu, Zhihua

AU - Liu, Yu

AU - Yu, Dianke

AU - Chang, Jiang

AU - Wei, Lixuan

AU - Gao, Yu Tang

AU - Koh, Woon Puay

AU - Xiang, Yong Bing

AU - Tang, Ze Zhong

AU - Fan, Jin Hu

AU - Han, Jing Jing

AU - Zhou, Sheng Li

AU - Zhang, Peng

AU - Zhang, Dong Yun

AU - Yuan, Yuan

AU - Huang, Ying

AU - Liu, Chunling

AU - Zhai, Kan

AU - Qiao, Yan

AU - Jin, Guangfu

AU - Guo, Chuanhai

AU - Fu, Jianhua

AU - Miao, Xiaoping

AU - Lu, Changdong

AU - Yang, Haijun

AU - Wang, Chaoyu

AU - Wheeler, William A.

AU - Gail, Mitchell

AU - Yeager, Meredith

AU - Yuenger, Jeff

AU - Guo, Er Tao

AU - Li, Ai Li

AU - Zhang, Wei

AU - Li, Xue Min

AU - Sun, Liang Dan

AU - Ma, Bao Gen

AU - Li, Yan

AU - Tang, Sa

AU - Peng, Xiu Qing

AU - Liu, Jing

AU - Hutchinson, Amy

AU - Jacobs, Kevin

AU - Giffen, Carol

AU - Burdette, Laurie

AU - Fraumeni, Joseph F.

AU - Shen, Hongbing

AU - Ke, Yang

AU - Zeng, Yixin

AU - Wu, Tangchun

AU - Kraft, Peter

AU - Chung, Charles C.

AU - Tucker, Margaret A.

AU - Hou, Zhi Chao

AU - Liu, Ya Li

AU - Hu, Yan Long

AU - Wang, Li

AU - Yuan, Guo

AU - Chen, Li Sha

AU - Liu, Xiao

AU - Ma, Teng

AU - Meng, Hui

AU - Li, Xin Min

AU - Ku, Jian Wei

AU - Zhou, Ying Fa

AU - Yang, Liu Qin

AU - Wang, Zhou

AU - Li, Yin

AU - Qige, Qirenwang

AU - Yang, Wen Jun

AU - Lei, Guang Yan

AU - Chen, Long Qi

AU - Li, En Min

AU - Yuan, Ling

AU - Yue, Wen Bin

AU - Wang, Ran

AU - Wang, Lu Wen

AU - Fan, Xue Ping

AU - Zhu, Fang Heng

AU - Zhao, Wei Xing

AU - Mao, Yi Min

AU - Zhang, Mei

AU - Xing, Guo Lan

AU - Li, Ji Lin

AU - Han, Min

AU - Ren, Jing Li

AU - Liu, Bin

AU - Ren, Shu Wei

AU - Kong, Qing Peng

AU - Li, Feng

AU - Sheyhidin, Ilyar

AU - Wei, Wu

AU - Zhang, Yan Rui

AU - Feng, Chang Wei

AU - Wang, Jin

AU - Yang, Yu Hua

AU - Hao, Hong Zhang

AU - Bao, Qi De

AU - Liu, Bao Chi

AU - Wu, Ai Qun

AU - Xie, Dong

AU - Yang, Wan Cai

AU - Wang, Liang

AU - Zhao, Xiao Hang

AU - Chen, Shu Qing

AU - Hong, Jun Yan

AU - Zhang, Xue Jun

AU - Freedman, Neal D.

AU - Goldstein, Alisa M.

AU - Lin, Dongxin

AU - Taylor, Philip R.

AU - Wang, Li Dong

AU - Chanock, Stephen J.

N1 - Funding Information: This work was funded by the National High-Tech Research and Development Program of China (2009AA022706 to D.L.), the National Basic Research Program of China (2011CB504303 to D.L. and W.T.) and the National Natural Science Foundation of China (30721001 to D.L., Q.Z. and Z.L.). We thank all the subjects and their family members whose contributions made this work possible; medical students from Zhengzhou University, Xinxiang Medical University, Zhengzhou Medical School and the Henan University of Science and Technology for sample and data collections; Q.C. Kan (The First Affiliated Hospital of Zhengzhou University) and Y. Xing (Xinxiang Medical University) for organizing field work for sample collection and finding financial support for the study; the Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, China, for genotyping; and W. Huang (Health Department of Henan Province) for field work organization. This work was supported by the Invitation Team of the Ministry of Education (2008IRTSTHN010), the National Natural Science Foundation of China (81071783), 863 High-Tech Key Projects (2012AA02A209, 2012AA02A503 and 2012AA02A201), Innovation Scientists and Technicians Troop Construction Projects of Henan Province (3047), the Key Disciplines Revitalization Plan of Zhengzhou University (20132016) and the Collaborative Innovation Center for Esophageal Cancer Research of Henan Province (20132016). The Shanghai Men’s Health Study (SMHS) was supported by NCI extramural research grant R01 CA82729. The Shanghai Women’s Health Study (SWHS) was supported by NCI extramural research grant R37 CA70837 and, in part, for biological sample collection, by NCI intramural research program contract NO2-CP-11010 with Vanderbilt University. The studies would not be possible without continuing support and devotion from the study participants and the staff of SMHS and SWHS. The Singapore Chinese Health Study (SCHS) was supported by NCI extramural research grants R01 CA55069, R35 CA53890, R01 CA80205 and R01 CA144034. We are indebted to the contributions of M.C. Yu and H.-P. Lee in the establishment of this cohort. The study would not be possible without the assistance in identifying cancer cases through database linkage provided by the Ministry of Health in Singapore. We are indebted to the study subjects for their continuing participation and to the staff of SCHS for their support. The Shanxi Upper Gastrointestinal Cancer Genetics Project was supported by NCI intramural research program contract NO2-SC-66211 with the Shanxi Cancer Hospital and Institute. The Nutrition Intervention Trials (NIT) was supported by NCI intramural research program contracts NO1-SC-91030 and HHSN261200477001C with the Cancer Institute and Hospital of the Chinese Academy of Medical Sciences. This research was supported in part by the intramural research program of the US NIH/NCI, the Division of Cancer Epidemiology and Genetics, and the Center for Cancer Research. This project was funded in part with federal funds from the US NIH/NCI under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US government. Publisher Copyright: © 2014 Nature America, Inc. All rights reserved.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84922352170&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922352170&partnerID=8YFLogxK

U2 - 10.1038/ng.3064

DO - 10.1038/ng.3064

M3 - Article

C2 - 25129146

AN - SCOPUS:84922352170

SN - 1061-4036

VL - 46

SP - 1001

EP - 1006

JO - Nature genetics

JF - Nature genetics

IS - 9

ER -

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

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