Genome-wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


Genome-wide association studies (GWAS) have identified 45 susceptibility loci associated with lung cancer. Only less than SNPs, small insertions and deletions (INDELs) are the second most abundant genetic polymorphisms in the human genome. INDELs are highly associated with multiple human diseases, including lung cancer. However, limited studies with large-scale samples have been available to systematically evaluate the effects of INDELs on lung cancer risk. Here, we performed a large-scale meta-analysis to evaluate INDELs and their risk for lung cancer in 23,202 cases and 19,048 controls. Functional annotations were performed to further explore the potential function of lung cancer risk INDELs. Conditional analysis was used to clarify the relationship between INDELs and SNPs. Four new risk loci were identified in genome-wide INDEL analysis (1p13.2: rs5777156, Insertion, OR = 0.92, p = 9.10 × 10−8; 4q28.2: rs58404727, Deletion, OR = 1.19, p = 5.25 × 10−7; 12p13.31: rs71450133, Deletion, OR = 1.09, p = 8.83 × 10−7; and 14q22.3: rs34057993, Deletion, OR = 0.90, p = 7.64 × 10−8). The eQTL analysis and functional annotation suggested that INDELs might affect lung cancer susceptibility by regulating the expression of target genes. After conducting conditional analysis on potential causal SNPs, the INDELs in the new loci were still nominally significant. Our findings indicate that INDELs could be potentially functional genetic variants for lung cancer risk. Further functional experiments are needed to better understand INDEL mechanisms in carcinogenesis.


  • Juncheng Dai
  • Mingtao Huang
  • Christopher I. Amos
  • Rayjean J. Hung
  • Adonina Tardon
  • Angeline Andrew
  • Chu Chen
  • David C. Christiani
  • Demetrius Albanes
  • Gadi Rennert
  • Jingyi Fan
  • Gary Goodman
  • Geoffrey Liu
  • John K. Field
  • Kjell Grankvist
  • Lambertus A. Kiemeney
  • Loic Le Marchand
  • Matthew B. Schabath
  • Mattias Johansson
  • Melinda C. Aldrich
  • Mikael Johansson
  • Neil Caporaso
  • Philip Lazarus
  • Stephan Lam
  • Stig E. Bojesen
  • Susanne Arnold
  • Maria Teresa Landi
  • Angela Risch
  • H. Erich Wichmann
  • Heike Bickeboller
  • Paul Brennan
  • Sanjay Shete
  • Shan Zienolddiny
  • Penella Woll
  • Victoria Stevens
  • Zhibin Hu
  • Hongbing Shen
Enheter & grupper
Externa organisationer
  • Nanjing Medical University
  • Baylor College of Medicine
  • Sinai Health System
  • University of Oviedo
  • Dartmouth-Hitchcock Medical Center
  • Fred Hutchinson Cancer Research Center
  • Harvard University
  • National Cancer Institute, NCI
  • Technion - Israel Institute of Technology
  • Swedish Medical Center
  • Princess Margaret Hospital University of Toronto
  • University of Liverpool
  • University of Hawaii Cancer Center
  • H. Lee Moffitt Cancer Center & Research Institute
  • International Agency for Research on Cancer, World Health Organization
  • British Columbia Cancer Agency
  • Copenhagen University Hospital
  • University of Copenhagen
  • University of Salzburg
  • Ludwig-Maximilian University of Munich
  • University Medical Center Göttingen
  • University of Texas
  • National Institute of Occupational Health, Norway
  • University of Sheffield
  • American Cancer Society
  • Radboud University Medical Center
  • Vanderbilt University Medical Center
  • Washington State University College of Pharmacy
  • University of Kentucky
  • Umeå University

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi


Sidor (från-till)2855-2864
Antal sidor10
TidskriftInternational Journal of Cancer
Utgåva nummer10
Tidigt onlinedatum2019 okt
StatusPublished - 2020 maj 15
Peer review utfördJa