Li, Y., Xiao, X., Han, Y. et al. (73 more authors) (2018) Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population. Carcinogenesis, 39 (3). pp. 336-346. ISSN 0143-3334
Abstract
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between SNPs and smoking status (never vs ever smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13,336 NSCLC cases. Candidate SNPs with p-value less than 0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with p-value less than 3.5x10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 NSCLC cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis p-value for these two SNPs were 1.24 with 6.96x10-7 and 1.37 with 3.49x10-7, respectively. Additionally, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and p-value of 8.12x10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 The Author(s). This is an author produced version of a paper subsequently published in Carcinogenesis. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) |
Funding Information: | Funder Grant number CANCER RESEARCH UK (CRUK) C43420/A14234 YORKSHIRE CANCER RESEARCH None |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 01 Nov 2017 10:07 |
Last Modified: | 13 Dec 2023 14:02 |
Status: | Published |
Publisher: | Oxford University Press |
Refereed: | Yes |
Identification Number: | 10.1093/carcin/bgx113 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:123285 |