Li, Yafang, Xiao, Xiangjun, Li, JianRong, Han, Younghun, Cheng, Chao, Fernandes, Gail F, Slewitzke, Shannon E, Rosenberg, Susan M, Zhu, Meng, Byun, Jinyoung et al (show 48 more authors)
(2024)
Lung cancer in ever- and never-smokers: findings from multi-population GWAS studies.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 33 (3).
pp. 389-399.
![[img]](https://livrepository.liverpool.ac.uk/style/images/fileicons/text.png) |
Text
Accepted manuscript.docx - Author Accepted Manuscript Available under License Creative Commons Attribution. Download (62kB) |
|
Text
Accepted Tables.docx - Author Accepted Manuscript Available under License Creative Commons Attribution. Download (29kB) |
|
Text
Accepted Figures.docx - Author Accepted Manuscript Available under License Creative Commons Attribution. Download (61MB) |
Abstract
<h4>Background</h4>Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer.<h4>Methods</h4>We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including eQTL colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer.<h4>Results</h4>Five novel independent loci, GABRA4, inter-genic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5x10-8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear <= 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior.<h4>Conclusions</h4>We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies.<h4>Impact</h4>Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiological insights into the complicated genetic architecture of this deadly cancer.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Lung Neoplasms, Smoking, Research Design, Genome-Wide Association Study, Smokers |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 07 Feb 2024 09:28 |
| Last Modified: | 16 Mar 2024 02:52 |
| DOI: | 10.1158/1055-9965.epi-23-0613 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178514 |
Dimensions
Dimensions
