Lung cancer in ever- and never-smokers: findings from multi-population GWAS studies.
| Title: | Lung cancer in ever- and never-smokers: findings from multi-population GWAS studies. |
|---|---|
| Authors: | Li, Yafang; Xiao, Xiangjun; Li, JianRong; Han, Younghun; Cheng, Chao; Fernandes, Gail F; Slewitzke, Shannon E; Rosenberg, Susan M; Zhu, Meng; Byun, Jinyoung; Bossé, Yohan; McKay, James D; Albanes, Demetrius; Lam, Stephen; Tardon, Adonina; Chen, Chu; Bojesen, Stig E; Landi, Maria Teresa; Johansson, Mattias; Risch, Angela; Bickeböller, Heike; Wichmann, H-Erich; Christiani, David C; Rennert, Gad; Arnold, Susanne M; Goodman, Gary E; Field, John K; Davies, Michael PA; Shete, Sanjay; Le Marchand, Loïc; Liu, Geoffrey; Hung, Rayjean J; Andrew, Angeline S; Kiemeney, Lambertus A; Sun, Ryan; Zienolddiny, Shanbeh; Grankvist, Kjell; Johansson, Mikael; Caporaso, Neil E; Cox, Angela; Hong, Yun-Chul; Lazarus, Philip; Schabath, Matthew B; Aldrich, Melinda C; Schwartz, Ann G; Gorlov, Ivan; Purrington, Kristen S; Yang, Ping; Liu, Yanhong; Bailey-Wilson, Joan E; Pinney, Susan M; Mandal, Diptasri; Willey, James C; Gaba, Colette; Brennan, Paul; Xia, Jun; Shen, Hongbing; Amos, Christopher I |
| Publisher Information: | American Association for Cancer Research (AACR) |
| Publication Year: | 2024 |
| Collection: | The University of Liverpool Repository |
| Description: | Background Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer. Methods 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. Results 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). Different risk patterns were observed for the variants among the different groups by smoking behavior. Conclusions We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies. Impact 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. |
| Document Type: | article in journal/newspaper |
| File Description: | text |
| Language: | English |
| ISSN: | 1055-9965 |
| Relation: | https://livrepository.liverpool.ac.uk/3178514/1/Accepted%20manuscript.docx; https://livrepository.liverpool.ac.uk/3178514/2/Accepted%20Tables.docx; https://livrepository.liverpool.ac.uk/3178514/3/Accepted%20Figures.docx; Collapse authors list. 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) , Bossé, Yohan, McKay, James D, Albanes, Demetrius, Lam, Stephen, Tardon, Adonina, Chen, Chu, Bojesen, Stig E, Landi, Maria Teresa, Johansson, Mattias, Risch, Angela, Bickeböller, Heike, Wichmann, H-Erich, Christiani, David C, Rennert, Gad, Arnold, Susanne M, Goodman, Gary E, Field, John K orcid:0000-0003-3951-6365 , Davies, Michael PA orcid:0000-0002-7609-4977 , Shete, Sanjay, Le Marchand, Loïc, Liu, Geoffrey, Hung, Rayjean J, Andrew, Angeline S, Kiemeney, Lambertus A, Sun, Ryan, Zienolddiny, Shanbeh, Grankvist, Kjell, Johansson, Mikael, Caporaso, Neil E, Cox, Angela, Hong, Yun-Chul, Lazarus, Philip, Schabath, Matthew B, Aldrich, Melinda C, Schwartz, Ann G, Gorlov, Ivan, Purrington, Kristen S, Yang, Ping, Liu, Yanhong, Bailey-Wilson, Joan E, Pinney, Susan M, Mandal, Diptasri, Willey, James C, Gaba, Colette, Brennan, Paul, Xia, Jun, Shen, Hongbing and Amos, Christopher I (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. ISSN 1055-9965, 1538-7755 |
| DOI: | 10.1158/1055-9965.epi-23-0613 |
| Availability: | https://livrepository.liverpool.ac.uk/3178514/; https://doi.org/10.1158/1055-9965.epi-23-0613; https://livrepository.liverpool.ac.uk/3178514/1/Accepted%20manuscript.docx; https://livrepository.liverpool.ac.uk/3178514/2/Accepted%20Tables.docx; https://livrepository.liverpool.ac.uk/3178514/3/Accepted%20Figures.docx |
| Rights: | cc_by_4 |
| Accession Number: | edsbas.F9CDA092 |
| Database: | BASE |