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Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population

Li, Yafang; Xiao, Xiangjun; Han, Younghun; Gorlova, Olga; Qian, David; Leighl, Natasha; Johansen, Jakob S.; Barnett, Matt; Chen, Chu and Goodman, Gary, et al. (2018) In Carcinogenesis 39(3). p.336-346
Abstract

Non-small cell lung cancer 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 single nucleotide polymorphisms (SNPs) and smoking status (never- versus 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 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13 970 controls. The significant SNPs with P-value <3.5 × 10-5... (More)

Non-small cell lung cancer 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 single nucleotide polymorphisms (SNPs) and smoking status (never- versus 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 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13 970 controls. The significant SNPs with P-value <3.5 × 10-5 (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 non-small cell lung cancer 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 6.96 × 10-7 and 1.37 with 3.49 × 10-7, respectively. In addition, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and P-value of 8.12 × 10-7. 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.

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Carcinogenesis
volume
39
issue
3
pages
11 pages
publisher
Oxford University Press
external identifiers
  • scopus:85043592947
ISSN
0143-3334
DOI
10.1093/carcin/bgx113
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English
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yes
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4354b0eb-88ad-4ca4-a85c-bd22fa04a78e
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2018-03-27 13:32:20
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2019-05-21 04:02:38
@article{4354b0eb-88ad-4ca4-a85c-bd22fa04a78e,
  abstract     = {<p>Non-small cell lung cancer 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 single nucleotide polymorphisms (SNPs) and smoking status (never- versus 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 non-small cell lung cancer cases. Candidate SNPs with P-value &lt;0.001 were further analyzed using a standard case-control interaction analysis including 13 970 controls. The significant SNPs with P-value &lt;3.5 × 10<sup>-5</sup> (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 non-small cell lung cancer 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 6.96 × 10<sup>-7</sup> and 1.37 with 3.49 × 10<sup>-7</sup>, respectively. In addition, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and P-value of 8.12 × 10<sup>-7</sup>. 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.</p>},
  author       = {Li, Yafang and Xiao, Xiangjun and Han, Younghun and Gorlova, Olga and Qian, David and Leighl, Natasha and Johansen, Jakob S. and Barnett, Matt and Chen, Chu and Goodman, Gary and Cox, Angela and Taylor, Fiona and Woll, Penella and Wichmann, H. Erich and Manz, Judith and Muley, Thomas and Risch, Angela and Rosenberger, Albert and Arnold, Susanne M. and Haura, Eric B. and Bolca, Ciprian and Holcatova, Ivana and Janout, Vladimir and Kontic, Milica and Lissowska, Jolanta and Mukeria, Anush and Ognjanovic, Simona and Orlowski, Tadeusz M. and Scelo, Ghislaine and Swiatkowska, Beata and Zaridze, David and Bakke, Per and Skaug, Vidar and Zienolddiny, Shanbeh and Duell, Eric J. and Butler, Lesley M. and Houlston, Richard and Artigas, María Soler and Grankvist, Kjell and Johansson, Mikael and Shepherd, Frances A. and Marcus, Michael W. and Brunnström, Hans and Manjer, Jonas and Melander, Olle and Muller, David C. and Overvad, Kim and Trichopoulou, Antonia and Tumino, Rosario and Liu, Geoffrey and Bojesen, Stig E. and Wu, Xifeng and Marchand, Loic Le and Albanes, Demetrios and Bickeböller, Heike and Aldrich, Melinda C. and Bush, William S. and Tardon, Adonina and Rennert, Gad and Dawn Teare, M. and Field, John K. and Kiemeney, Lambertus A. and Lazarus, Philip and Haugen, Aage and Lam, Stephen and Schabath, Matthew B. and Andrew, Angeline S. and Bertazzi, Pier Alberto and Pesatori, Angela C. and Christiani, David C. and Caporaso, Neil and Johansson, Mattias and McKay, James D. and Brennan, Paul and Hung, Rayjean J. and Amos, Christopher I.},
  issn         = {0143-3334},
  language     = {eng},
  month        = {03},
  number       = {3},
  pages        = {336--346},
  publisher    = {Oxford University Press},
  series       = {Carcinogenesis},
  title        = {Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population},
  url          = {http://dx.doi.org/10.1093/carcin/bgx113},
  volume       = {39},
  year         = {2018},
}