title: A genome-wide gene-environment interaction analysis for tobacco smoke and lung cancer susceptibility.
abstract: Tobacco smoke is the major environmental risk factor underlying lung carcinogenesis. However, approximately one-tenth smokers develop lung cancer in their lifetime indicating there is significant individual variation in susceptibility to lung cancer. And, the reasons for this are largely unknown. In particular, the genetic variants discovered in genome-wide association studies (GWAS) account for only a small fraction of the phenotypic variations for lung cancer, and gene-environment interactions are thought to explain the missing fraction of disease heritability. The ability to identify smokers at high risk of developing cancer has substantial preventive implications. Thus, we undertook a gene-smoking interaction analysis in a GWAS of lung cancer in Han Chinese population using a two-phase designed case-control study. In the discovery phase, we evaluated all pair-wise (591 370) gene-smoking interactions in 5408 subjects (2331 cases and 3077 controls) using a logistic regression model with covariate adjustment. In the replication phase, promising interactions were validated in an independent population of 3023 subjects (1534 cases and 1489 controls). We identified interactions between two single nucleotide polymorphisms and smoking. The interaction P values are 6.73 × 10(-) (6) and 3.84 × 10(-) (6) for rs1316298 and rs4589502, respectively, in the combined dataset from the two phases. An antagonistic interaction (rs1316298-smoking) and a synergetic interaction (rs4589502-smoking) were observed. The two interactions identified in our study may help explain some of the missing heritability in lung cancer susceptibility and present strong evidence for further study of these gene-smoking interactions, which are benefit to intensive screening and smoking cessation interventions.
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ruyang
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Chu
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Molecular Oncology and Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.affiliation: Institute of Occupational Medicine and Ministry of Education, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Guo
authors.affiliation: Bio-X Center and Affiliated Changning Mental Health Center, Ministry of Education Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yongyue
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Yi
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jianling
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jianhang
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chongqi
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Institute of Occupational Medicine and Ministry of Education, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China, Section of Clinical Epidemiology, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing 210029, China and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Molecular Oncology and Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China, Section of Clinical Epidemiology, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing 210029, China and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China, fengchen@njmu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
mesh_terms: D000465:Algorithms; D016022:Case-Control Studies; D002681:China; D005500:Follow-Up Studies; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000150:complications / Q000235:genetics; D014026:Nicotiana