Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperLetterResearchpeer-review

DOI

  • James D McKay, UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization
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  • Rayjean J Hung, University of Toronto, St. Michael's Hospital, Toronto
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  • Younghun Han, Dartmouth College
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  • Xuchen Zong, University of Toronto, St. Michael's Hospital, Toronto
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  • Robert Carreras-Torres, UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization
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  • David C Christiani, Harvard University
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  • Neil E. Caporaso, NCI, NIH National Cancer Institute (NCI), National Institutes of Health (NIH) - USA, NIH, Mol Targeting Sect, Radiat Oncol Branch
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  • Mattias Johansson, UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization
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  • Xiangjun Xiao, Dartmouth College
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  • Yafang Li, Dartmouth College
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  • Jinyoung Byun, Dartmouth College
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  • Alison Dunning, Cambridge University
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  • Karen A Pooley, Cambridge University
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  • David C. Qian, Dartmouth College
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  • Xuemei Ji, Dartmouth College
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  • Geoffrey Liu, University of Toronto, St. Michael's Hospital, Toronto
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  • Maria N. Timofeeva, UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization
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  • Stig E. Bojesen, Herlev & Gentofte Hosp
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  • Xifeng Wu, UTMD Anderson Cancer Center
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  • Loic Le Marchand, Univ Hawaii, University of Hawaii System, Inst Astron
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  • Demetrios Albanes, NCI, NIH National Cancer Institute (NCI), National Institutes of Health (NIH) - USA, NIH, Mol Targeting Sect, Radiat Oncol Branch
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  • Heike Bickeböller, Univ Gottingen, University of Gottingen, Inst Astrophys
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  • Melinda C. Aldrich, Vanderbilt University
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  • William S. Bush, Case Western Reserve University
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  • Adonina Tardón, CIBER Epidemiology and Public Health CIBERESP
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  • Gad Rennert, Technion - Israel Institute of Technology
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  • M. Dawn Teare, University of Sheffield, Sheffield
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  • John K Field, University Liverpool
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  • Lambertus A Kiemeney, Radboud University Nijmegen
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  • Philip Lazarus, Washington State University Pullman
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  • Aage Haugen, Nat Inst Occupat Hlth
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  • Stephen T Lam, British Columbia Canc Agcy
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  • Matthew B. Schabath, Department of Surgery, H. Lee Moffitt Cancer Center and Research Institute
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  • Angeline S Andrew, Dartmouth College
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  • Hongbing Shen, Stomatological School and Hospital, Nanjing Medical University
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  • Yun-Chul Hong, Seoul National University
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  • Jian-Min Yuan, University of Pittsburgh School of Med., Pittsburgh
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  • Pier Alberto Bertazzi, University of Milan, Milan, Italy
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  • Angela Cecilia Pesatori, University of Milan, Milan, Italy
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  • Yuanqing Ye, UTMD Anderson Cancer Center
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  • Nancy Diao, Harvard University
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  • Li Su, Harvard University
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  • Ruyang Zhang, Harvard University
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  • Yonathan Brhane, University of Toronto, St. Michael's Hospital, Toronto
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  • Natasha Leighl, University of Toronto, St. Michael's Hospital, Toronto
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  • Jakob S. Johansen, Copenhagen University Hospital, Copenhagen
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  • Anders Mellemgaard, Copenhagen University Hospital, Copenhagen
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  • Walid Saliba, Technion - Israel Institute of Technology
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  • Kim Overvad
  • Mikael Johansson, Umea Univ, Umea University, Dept Radiat Sci, Umeá University, Umeá
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  • SpiroMeta Consortium

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genomewide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.

Original languageEnglish
JournalNature Genetics
Volume49
Issue7
Pages (from-to)1126-+
Number of pages9
ISSN1061-4036
DOIs
Publication statusPublished - Jul 2017

    Research areas

  • GENOME-WIDE ASSOCIATION, TELOMERE LENGTH, CROHNS-DISEASE, COMMON CANCERS, GLIOMA RISK, VARIANTS, IMPUTATION, ARCHITECTURE, METAANALYSIS, CONSORTIUM

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