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Olle Melander

Principal investigator

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

Author

  • James D. McKay
  • Rayjean J. Hung
  • Younghun Han
  • Xuchen Zong
  • Robert Carreras-Torres
  • David C. Christiani
  • Neil E Caporaso
  • Mattias Johansson
  • Xiangjun Xiao
  • Yafang Li
  • Jinyoung Byun
  • Alison Dunning
  • Karen A Pooley
  • David C Qian
  • Xuemei Ji
  • Geoffrey Liu
  • Maria N Timofeeva
  • Stig E. Bojesen
  • Xifeng Wu
  • Loic Le Marchand
  • Demetrios Albanes
  • Heike Bickeböller
  • Melinda C Aldrich
  • William S Bush
  • Adonina Tardon
  • Gad Rennert
  • M Dawn Teare
  • John K. Field
  • Lambertus A. Kiemeney
  • Philip Lazarus
  • Aage Haugen
  • Stephen Lam
  • Matthew B Schabath
  • Angeline S Andrew
  • Hongbing Shen
  • Yun-Chul Hong
  • Jian-Min Yuan
  • Pier Alberto Bertazzi
  • Angela C Pesatori
  • Yuanqing Ye
  • Nancy Diao
  • Li Su
  • Ruyang Zhang
  • Yonathan Brhane
  • Natasha Leighl
  • Jakob S Johansen
  • Hans Brunnström
  • Jonas Manjer
  • Olle Melander
  • Lei Song

Summary, in English

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 genome-wide 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.

Department/s

  • Tumor microenvironment
  • Surgery
  • Cardiovascular Research - Hypertension
  • EpiHealth: Epidemiology for Health

Publishing year

2017-07

Language

English

Pages

1126-1132

Publication/Series

Nature Genetics

Volume

49

Issue

7

Document type

Journal article (letter)

Publisher

Nature Publishing Group

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Surgery
  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 1546-1718