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A Novel Genetic Variant in Long Non-coding RNA Gene NEXN-AS1 is Associated with Risk of Lung Cancer.

About this Publication
Title
A Novel Genetic Variant in Long Non-coding RNA Gene NEXN-AS1 is Associated with Risk of Lung Cancer.
Pubmed ID
27713484 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Sci Rep. 2016 Oct 7; Volume 6: Pages 34234
Authors
Yuan H, Liu H, Liu Z, Owzar K, Han Y, Su L, Wei Y, Hung RJ, McLaughlin J, Brhane Y, Brennan P, Bickeboeller H, Rosenberger A, Houlston RS, Caporaso N, Landi MT, Heinrich J, Risch A, Christiani DC, Gümüş ZH, ...show more Klein RJ, Amos CI, Wei Q
Affiliations
  • 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.
  • Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NC, USA.
  • Massachusetts General Hospital, Boston, Massachusetts, USA.
  • Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
  • Public Health Ontario, Toronto, Ontario, Canada.
  • Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), Lyon, France.
  • Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
  • Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
...show more
  • Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Helmholtz Centre Munich, German Research Centre for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany.
  • Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
  • Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, USA.
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.

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