Dai, J., Huang, M., Amos, C.I. et al. (36 more authors) (2020) Genome‐wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk. International Journal of Cancer, 146 (10). pp. 2855-2864. ISSN 0020-7136
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 UICC. This is an author-produced version of a paper subsequently published in International Journal of Cancer. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | INDELs; Lung cancer; Genome-wide association studies (GWAS) |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Human Metabolism (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Oncology (Sheffield) |
Funding Information: | Funder Grant number Weston Park Hospital Cancer Charity CA115 Sheffield Hospitals Charitable Trust (Special Trustees) 091002 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 15 Oct 2019 11:21 |
Last Modified: | 16 Dec 2021 13:52 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/ijc.32698 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:152155 |