title: Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations.
abstract: To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (P < 5 × 10-8), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21.3, BTNL2) which is specific to cases with EGFR mutations. In further sub-analyses by EGFR status, rs9387478 (ROS1/DCBLD1) and rs2179920 (HLA-DPB1) showed stronger estimated associations in EGFR-positive compared to EGFR-negative cases. Comparison of the overall associations with published results in Western populations revealed that the majority of these findings were distinct, underscoring the importance of distinct contributing factors for smoking and non-smoking lung cancer. Our results extend the catalogue of regions associated with lung adenocarcinoma in non-smoking Asian women and highlight the importance of how the germline could inform risk for specific tumour mutation patterns, which could have important translational implications.
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authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Division of Thoracic Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
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authors.initials: CY
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authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands.
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authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.|State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
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authors.initials: M
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authors.affiliation: Genomic Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Yao-Jen
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authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.|State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Hongyan
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authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.|State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Li
authors.initials: L
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authors.affiliation: Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Yen-Li
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authors.affiliation: Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Ying-Hsiang
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authors.forename: Jie
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authors.affiliation: Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
authors.forename: Taiki
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authors.forename: Yang
authors.initials: Y
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authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.|Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc, Gaithersburg, MD, USA.
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authors.initials: B
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authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.|Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc, Gaithersburg, MD, USA.
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authors.initials: K
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authors.initials: SA
authors.lastname: Li
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
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authors.initials: Z
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authors.affiliation: Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, People's Republic of China.
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authors.initials: S
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authors.affiliation: Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People's Republic of China.|Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, People's Republic of China.
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authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People's Republic of China.|Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, People's Republic of China.
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authors.forename: Taichi
authors.initials: T
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authors.affiliation: Shanghai Pulmonary Hospital, Shanghai, People's Republic of China.
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authors.initials: CN
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authors.initials: D
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authors.initials: K
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authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.|Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
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authors.initials: H
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authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
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authors.initials: N
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authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
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authors.initials: T
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authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
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authors.initials: SJ
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mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D034961:Antigens, Nuclear / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D000071797:Butyrophilins / Q000235:genetics*; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D018095:Germ-Line Mutation; D059868:HLA-DP beta-Chains / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012727:Sex Characteristics; D012907:Smoking / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics; D000092468:Bromodomain Containing Proteins
chemical_list: D034961:Antigens, Nuclear; D000071797:Butyrophilins; D066246:ErbB Receptors; D059868:HLA-DP beta-Chains; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C408263:BTNL2 protein, human; C436326:DCBLD2 protein, human; C071170:HLA-DPB1 antigen; C406238:fetal Alzheimer antigen; D000092468:Bromodomain Containing Proteins; C512478:EGFR protein, human