TY - JOUR
T1 - Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions
AU - Wu, Chen
AU - Kraft, Peter
AU - Zhai, Kan
AU - Chang, Jiang
AU - Wang, Zhaoming
AU - Li, Yun
AU - Hu, Zhibin
AU - He, Zhonghu
AU - Jia, Weihua
AU - Abnet, Christian C.
AU - Liang, Liming
AU - Hu, Nan
AU - Miao, Xiaoping
AU - Zhou, Yifeng
AU - Liu, Zhihua
AU - Zhan, Qimin
AU - Liu, Yu
AU - Qiao, Yan
AU - Zhou, Yuling
AU - Jin, Guangfu
AU - Guo, Chuanhai
AU - Lu, Changdong
AU - Yang, Haijun
AU - Fu, Jianhua
AU - Yu, Dianke
AU - Freedman, Neal D.
AU - Ding, Ti
AU - Tan, Wen
AU - Goldstein, Alisa M.
AU - Wu, Tangchun
AU - Shen, Hongbing
AU - Ke, Yang
AU - Zeng, Yixin
AU - Chanock, Stephen J.
AU - Taylor, Philip R.
AU - Lin, Dongxin
N1 - Funding Information:
This work was funded by the National HighTech Research and Development Program of China (2009AA022706 to D.L.), the National Basic Research Program of China (2011CB504303 to D.L. and W.T.), the National Natural Science Foundation of China (30721001 to D.L., Q.Z. and Z.L.) and the Intramural Research Program of the US National Institutes of Health, NCI and the Division of Cancer Epidemiology and Genetics.
PY - 2012/10
Y1 - 2012/10
N2 - We conducted a genome-wide association study (GWAS) and a genome-wide gene-environment interaction analysis of esophageal squamous-cell carcinoma (ESCC) in 2,031 affected individuals (cases) and 2,044 controls with independent validation in 8,092 cases and 8,620 controls. We identified nine new ESCC susceptibility loci, of which seven, at chromosomes 4q23, 16q12.1, 17q21, 22q12, 3q27, 17p13 and 18p11, had a significant marginal effect (P = 1.78 × 10-39 to P = 2.49 × 10-11) and two of which, at 2q22 and 13q33, had a significant association only in the gene-alcohol drinking interaction (gene-environment interaction P (P G × E) = 4.39 × 10-11 and P G × E = 4.80 × 10-8, respectively). Variants at the 4q23 locus, which includes the ADH cluster, each had a significant interaction with alcohol drinking in their association with ESCC risk (P G × E = 2.54 × 10-7 to P G × E = 3.23 × 10-2). We confirmed the known association of the ALDH2 locus on 12q24 to ESCC, and a joint analysis showed that drinkers with both of the ADH1B and ALDH2 risk alleles had a fourfold increased risk for ESCC compared to drinkers without these risk alleles. Our results underscore the direct genetic contribution to ESCC risk, as well as the genetic contribution to ESCC through interaction with alcohol consumption.
AB - We conducted a genome-wide association study (GWAS) and a genome-wide gene-environment interaction analysis of esophageal squamous-cell carcinoma (ESCC) in 2,031 affected individuals (cases) and 2,044 controls with independent validation in 8,092 cases and 8,620 controls. We identified nine new ESCC susceptibility loci, of which seven, at chromosomes 4q23, 16q12.1, 17q21, 22q12, 3q27, 17p13 and 18p11, had a significant marginal effect (P = 1.78 × 10-39 to P = 2.49 × 10-11) and two of which, at 2q22 and 13q33, had a significant association only in the gene-alcohol drinking interaction (gene-environment interaction P (P G × E) = 4.39 × 10-11 and P G × E = 4.80 × 10-8, respectively). Variants at the 4q23 locus, which includes the ADH cluster, each had a significant interaction with alcohol drinking in their association with ESCC risk (P G × E = 2.54 × 10-7 to P G × E = 3.23 × 10-2). We confirmed the known association of the ALDH2 locus on 12q24 to ESCC, and a joint analysis showed that drinkers with both of the ADH1B and ALDH2 risk alleles had a fourfold increased risk for ESCC compared to drinkers without these risk alleles. Our results underscore the direct genetic contribution to ESCC risk, as well as the genetic contribution to ESCC through interaction with alcohol consumption.
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U2 - 10.1038/ng.2411
DO - 10.1038/ng.2411
M3 - Article
C2 - 22960999
AN - SCOPUS:84866919001
SN - 1061-4036
VL - 44
SP - 1090
EP - 1097
JO - Nature genetics
JF - Nature genetics
IS - 10
ER -