title: A Novel Genetic Variant in Long Non-coding RNA Gene NEXN-AS1 is Associated with Risk of Lung Cancer.
abstract: Lung cancer etiology is multifactorial, and growing evidence has indicated that long non-coding RNAs (lncRNAs) are important players in lung carcinogenesis. We performed a large-scale meta-analysis of 690,564 SNPs in 15,531 autosomal lncRNAs by using datasets from six previously published genome-wide association studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung (TRICL) consortium in populations of European ancestry. Previously unreported significant SNPs (P value < 1 × 10-7) were further validated in two additional independent lung cancer GWAS datasets from Harvard University and deCODE. In the final meta-analysis of all eight GWAS datasets with 17,153 cases and 239,337 controls, a novel risk SNP rs114020893 in the lncRNA NEXN-AS1 region at 1p31.1 remained statistically significant (odds ratio = 1.17; 95% confidence interval = 1.11-1.24; P = 8.31 × 10-9). In further in silico analysis, rs114020893 was predicted to change the secondary structure of the lncRNA. Our finding indicates that SNP rs114020893 of NEXN-AS1 at 1p31.1 may contribute to lung cancer susceptibility.
authors.affiliation: Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.|Department of Medicine, Duke University School of Medicine, Durham, NC, USA.|Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC, USA.|Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC, USA.|Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Kouros
authors.initials: K
authors.lastname: Owzar
authors.affiliation: Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NC, USA.
authors.forename: Younghun
authors.initials: Y
authors.lastname: Han
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Yongyue
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Rayjean J
authors.initials: RJ
authors.lastname: Hung
authors.affiliation: Public Health Ontario, Toronto, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: McLaughlin
authors.affiliation: Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Yonathan
authors.initials: Y
authors.lastname: Brhane
authors.affiliation: Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.affiliation: Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Bickeboeller
authors.affiliation: Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Rosenberger
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.affiliation: Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Caporaso
authors.affiliation: Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Landi
authors.affiliation: Helmholtz Centre Munich, German Research Centre for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany.|Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital Munich, Ludwig Maximilian University Munich, Munich, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Heinrich
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.|Department of Epigenomics and Cancer Risk Factors, DKFZ-German Cancer Research Center, Heidelberg, Germany.|Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Risch
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Zeynep H
authors.initials: ZH
authors.lastname: Gümüş
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Klein
authors.affiliation: Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NC, USA.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC, USA.|Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding / Q000235:genetics*; D012307:Risk Factors
chemical_list: D062085:RNA, Long Noncoding