title: Systematical analyses of variants in CTCF-binding sites identified a novel lung cancer susceptibility locus among Chinese population.
abstract: Genome-wide association studies identified genetic susceptibility variants mostly lie outside of protein-coding regions. It suggested variants located at transcriptional regulatory region should play an important role in cancer carcinogenesis including lung cancer. In the present study, we systematically investigated the associations between the variants in the binding sites of an extensive transcription factor CTCF and lung cancer risk in Chinese population. A two-stage case-control design was conducted to evaluate the variants located at the uniform CTCF ChIP-seq peaks in a Chinese population (2,331 vs 3,077; 1,115 vs 1,346). The ChIP-seq data for CTCF, specified on lung cancer cell line A549, were downloaded from ENCODE database. Imputation was performed to increase the genome coverage in the CTCF binding regions. Three variants in CTCF binding sites were found to associate with lung cancer risk in the first stage. Further replication revealed a novel single nucleotide polymorphism rs60507107 was significantly associated with increased risk of lung cancer in two stages (Additive model: OR = 1.19, 95%CI = 1.11-1.27, P = 6.98 × 10(-7)). Our results indicate that rs60507107 in the binding site of CTCF is associated with an increased risk of lung cancer. This may further advance our understanding of regulatory DNA sequences in cancer development.
authors.affiliation: 1] Department of Epidemiology and Biostatistics and Ministry of Education (MOE), Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China [2] Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE), Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE), Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE), Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE), Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE), Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education (MOE), Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: 1] Department of Epidemiology and Biostatistics and Ministry of Education (MOE), Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China [2] Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.affiliation: 1] Department of Epidemiology and Biostatistics and Ministry of Education (MOE), Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China [2] Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.affiliation: 1] Department of Epidemiology and Biostatistics and Ministry of Education (MOE), Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China [2] Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China [3] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, 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: 1] Department of Epidemiology and Biostatistics and Ministry of Education (MOE), Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China [2] Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China [3] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D044466:Asian People / Q000235:genetics*; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002681:China; D047369:Chromatin Immunoprecipitation; D030541:Databases, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D012097:Repressor Proteins