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

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. AldrichMikael 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, Olle Melander, Hans Brunnstrom, Shan Zienolddiny, Penella Woll, Victoria Stevens, Zhibin Hu, Hongbing Shen

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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.

Original languageEnglish
Pages (from-to)2855-2864
Number of pages10
JournalInternational Journal of Cancer
Issue number10
StatePublished - May 15 2020

Bibliographical note

Funding Information:
We thank the study participants and research staff for their contributions and commitment to our study. This work was supported by the National Natural Science of China (81521004, 81820108028), the Priority Academic Program for the Development of Jiangsu Higher Education Institutions [Public Health and Preventive Medicine], Top‐notch Academic Programs Project of Jiangsu Higher Education Institutions (PPZY2015A067) and the National Institutes of Health and the National Cancer Institute (CA209414 and CA092824 to D.C.C.).

Publisher Copyright:
© 2019 UICC


  • INDELs
  • genome-wide association studies
  • lung cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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