title: Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.
abstract: 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 (PG×E)=4.39×10(-11) and PG×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 (PG×E=2.54×10(-7) to PG×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.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Kan
authors.initials: K
authors.lastname: Zhai
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Zhonghu
authors.initials: Z
authors.lastname: He
authors.forename: Weihua
authors.initials: W
authors.lastname: Jia
authors.forename: Christian C
authors.initials: CC
authors.lastname: Abnet
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Liu
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Qiao
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zhou
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Guo
authors.forename: Changdong
authors.initials: C
authors.lastname: Lu
authors.forename: Haijun
authors.initials: H
authors.lastname: Yang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Fu
authors.forename: Dianke
authors.initials: D
authors.lastname: Yu
authors.forename: Neal D
authors.initials: ND
authors.lastname: Freedman
authors.forename: Ti
authors.initials: T
authors.lastname: Ding
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.forename: Yang
authors.initials: Y
authors.lastname: Ke
authors.forename: Yixin
authors.initials: Y
authors.lastname: Zeng
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000428:Alcohol Drinking / Q000009:adverse effects; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D044466:Asian People; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000209:etiology / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial