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Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

Author

Listed:
  • Xuemei Ji

    (Geisel School of Medicine at Dartmouth)

  • Yohan Bossé

    (Laval University
    Institut universitaire de cardiologie et de pneumologie de Québec)

  • Maria Teresa Landi

    (National Institutes of Health)

  • Jiang Gui

    (Geisel School of Medicine at Dartmouth)

  • Xiangjun Xiao

    (Geisel School of Medicine at Dartmouth)

  • David Qian

    (Geisel School of Medicine at Dartmouth)

  • Philippe Joubert

    (Institut universitaire de cardiologie et de pneumologie de Québec)

  • Maxime Lamontagne

    (Institut universitaire de cardiologie et de pneumologie de Québec)

  • Yafang Li

    (Geisel School of Medicine at Dartmouth)

  • Ivan Gorlov

    (Geisel School of Medicine at Dartmouth)

  • Mariella Biasi

    (University of Pennsylvania
    University of Pennsylvania)

  • Younghun Han

    (Geisel School of Medicine at Dartmouth)

  • Olga Gorlova

    (Geisel School of Medicine at Dartmouth)

  • Rayjean J. Hung

    (Sinai Health System and University of Toronto)

  • Xifeng Wu

    (The University of Texas MD Anderson Cancer Center)

  • James McKay

    (World Health Organization)

  • Xuchen Zong

    (Sinai Health System and University of Toronto)

  • Robert Carreras-Torres

    (World Health Organization)

  • David C. Christiani

    (Harvard School of Public Health
    Massachusetts General Hospital)

  • Neil Caporaso

    (National Institutes of Health)

  • Mattias Johansson

    (World Health Organization)

  • Geoffrey Liu

    (Sinai Health System and University of Toronto)

  • Stig E. Bojesen

    (Copenhagen University Hospital
    University of Copenhagen
    Herlev and Gentofte Hospital)

  • Loic Marchand

    (University of Hawaii Cancer Center)

  • Demetrios Albanes

    (National Institutes of Health)

  • Heike Bickeböller

    (Georg-August-University Göttingen)

  • Melinda C. Aldrich

    (Vanderbilt University Medical Center)

  • William S. Bush

    (Vanderbilt University Medical Center
    Case Western Reserve University)

  • Adonina Tardon

    (University of Oviedo
    Campus del Cristo s/n)

  • Gad Rennert

    (Carmel Medical Center
    Technion)

  • Chu Chen

    (Fred Hutchinson Cancer Research Center)

  • M. Dawn Teare

    (University of Sheffield)

  • John K. Field

    (University of Liverpool)

  • Lambertus A. Kiemeney

    (Radboud Institute for Health Sciences)

  • Philip Lazarus

    (Washington State University)

  • Aage Haugen

    (National Institute of Occupational Health)

  • Stephen Lam

    (British Columbia Cancer Agency)

  • Matthew B. Schabath

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Angeline S. Andrew

    (Geisel School of Medicine)

  • Hongbing Shen

    (Nanjing Medical University)

  • Yun-Chul Hong

    (Seoul National University College of Medicine)

  • Jian-Min Yuan

    (University of Pittsburgh Cancer Institute)

  • Pier A. Bertazzi

    (IRCCS Foundation Ca’Granda Ospedale Maggiore Policlinico
    University of Milan)

  • Angela C. Pesatori

    (IRCCS Foundation Ca’Granda Ospedale Maggiore Policlinico
    University of Milan)

  • Yuanqing Ye

    (The University of Texas MD Anderson Cancer Center)

  • Nancy Diao

    (Harvard School of Public Health)

  • Li Su

    (Harvard School of Public Health)

  • Ruyang Zhang

    (Harvard School of Public Health
    Nanjing Medical University)

  • Yonathan Brhane

    (Sinai Health System and University of Toronto)

  • Natasha Leighl

    (University Health Network—The Princess Margaret Cancer Centre)

  • Jakob S. Johansen

    (Copenhagen University Hospital)

  • Anders Mellemgaard

    (Copenhagen University Hospital)

  • Walid Saliba

    (Carmel Medical Center
    Technion)

  • Christopher Haiman

    (University of Southern California Norris Comprehensive Cancer Center)

  • Lynne Wilkens

    (University of Hawaii Cancer Center)

  • Ana Fernandez-Somoano

    (University of Oviedo
    Campus del Cristo s/n)

  • Guillermo Fernandez-Tardon

    (University of Oviedo
    Campus del Cristo s/n)

  • Erik H. F. M. Heijden

    (Radboud Institute for Health Sciences)

  • Jin Hee Kim

    (Sejong University)

  • Juncheng Dai

    (Nanjing Medical University)

  • Zhibin Hu

    (Nanjing Medical University)

  • Michael P. A. Davies

    (University of Liverpool)

  • Michael W. Marcus

    (University of Liverpool)

  • Hans Brunnström

    (Lund University)

  • Jonas Manjer

    (Lund University)

  • Olle Melander

    (Lund University)

  • David C. Muller

    (Imperial College London)

  • Kim Overvad

    (Lund University)

  • Antonia Trichopoulou

    (Hellenic Health Foundation)

  • Rosario Tumino

    (“Civic-M.P. Arezzo” Hospital, ASP)

  • Jennifer Doherty

    (Geisel School of Medicine
    Fred Hutchinson Cancer Research Center)

  • Gary E. Goodman

    (Fred Hutchinson Cancer Research Center
    Swedish Medical Group)

  • Angela Cox

    (University of Sheffield)

  • Fiona Taylor

    (University of Sheffield)

  • Penella Woll

    (University of Sheffield)

  • Irene Brüske

    (German Research Center for Environmental Health)

  • Judith Manz

    (German Research Center for Environmental Health)

  • Thomas Muley

    (Thoraxklinik at University Hospital Heidelberg
    Translational Lung Research Center Heidelberg (TLRC-H))

  • Angela Risch

    (University of Salzburg)

  • Albert Rosenberger

    (Georg-August-University Göttingen)

  • Kjell Grankvist

    (Umeå University)

  • Mikael Johansson

    (Umeå University)

  • Frances Shepherd

    (Princess Margaret Cancer Centre)

  • Ming-Sound Tsao

    (Princess Margaret Cancer Centre)

  • Susanne M. Arnold

    (University of Kentucky)

  • Eric B. Haura

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Ciprian Bolca

    (Institute of Pneumology “Marius Nasta”)

  • Ivana Holcatova

    (Charles University)

  • Vladimir Janout

    (Charles University)

  • Milica Kontic

    (University of Belgrade)

  • Jolanta Lissowska

    (M. Sklodowska-Curie Institute—Oncology Center)

  • Anush Mukeria

    (Russian N.N. Blokhin Cancer Research Centre)

  • Simona Ognjanovic

    (International Organization for Cancer Prevention and Research)

  • Tadeusz M. Orlowski

    (National Tuberculosis and Lung Diseases Research Institute)

  • Ghislaine Scelo

    (World Health Organization)

  • Beata Swiatkowska

    (Nofer Institute of Occupational Medicine)

  • David Zaridze

    (Russian N.N. Blokhin Cancer Research Centre)

  • Per Bakke

    (University of Bergen)

  • Vidar Skaug

    (National Institute of Occupational Health)

  • Shanbeh Zienolddiny

    (National Institute of Occupational Health)

  • Eric J. Duell

    (Catalan Institute of Oncology (ICO-IDIBELL))

  • Lesley M. Butler

    (University of Pittsburgh Cancer Institute)

  • Woon-Puay Koh

    (Duke–NUS Medical School
    National University of Singapore)

  • Yu-Tang Gao

    (Shanghai Cancer Institute)

  • Richard Houlston

    (The Institute of Cancer Research)

  • John McLaughlin

    (Public Health Ontario)

  • Victoria Stevens

    (American Cancer Society, Inc.)

  • David C. Nickle

    (Merck Research Laboratories)

  • Ma’en Obeidat

    (The University of British Columbia)

  • Wim Timens

    (University Medical Center Groningen)

  • Bin Zhu

    (National Institutes of Health)

  • Lei Song

    (National Institutes of Health)

  • María Soler Artigas

    (University of Leicester
    Glenfield Hospital)

  • Martin D. Tobin

    (University of Leicester
    Glenfield Hospital)

  • Louise V. Wain

    (University of Leicester
    Glenfield Hospital)

  • Fangyi Gu

    (National Institutes of Health)

  • Jinyoung Byun

    (Geisel School of Medicine at Dartmouth)

  • Ahsan Kamal

    (Geisel School of Medicine at Dartmouth)

  • Dakai Zhu

    (Geisel School of Medicine at Dartmouth)

  • Rachel F. Tyndale

    (University of Toronto
    University of Toronto
    Centre for Addiction and Mental Health)

  • Wei-Qi Wei

    (Vanderbilt University)

  • Stephen Chanock

    (National Institutes of Health)

  • Paul Brennan

    (World Health Organization)

  • Christopher I. Amos

    (Geisel School of Medicine at Dartmouth
    Baylor College of Medicine)

Abstract

Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.

Suggested Citation

  • Xuemei Ji & Yohan Bossé & Maria Teresa Landi & Jiang Gui & Xiangjun Xiao & David Qian & Philippe Joubert & Maxime Lamontagne & Yafang Li & Ivan Gorlov & Mariella Biasi & Younghun Han & Olga Gorlova & , 2018. "Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05074-y
    DOI: 10.1038/s41467-018-05074-y
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