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Title: Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population
Author: Li, Yafang
Xiao, Xiangjun
Han, Younghun
Gorlova, Olga
Qian, David
Leighl, Natasha
Johansen, Jakob S.
Barnett, Matt
Chen, Chu
Goodman, Gary
Cox, Angela
Taylor, Fiona
Woll, Penella
Wichmann, H.-Erich
Manz, Judith
Muley, Thomas
Risch, Angela
Rosenberger, Albert
Arnold, Susanne M.
Haura, Eric B.
Bolca, Ciprian
Holcatova, Ivana
Janout, Vladimir
Kontic, Milica
Lissowska, Jolanta
Mukeria, Anush
Ognjanovic, Simona
Orlowski, Tadeusz M.
Scelo, Ghislaine
Swiatkowska, Beata
Zaridze, David
Bakke, Per
Skaug, Vidar
Zienolddiny, Shanbeh
Duell, Eric J.
Butler, Lesley M.
Houlston, Richard
Soler Artigas, María
Grankvist, Kjell
Johansson, Mikael
Shepherd, Frances A.
Marcus, Michael W.
Brunnström, Hans
Manjer, Jonas
Melander, Olle
Muller, David C.
Overvad, Kim
Trichopoulou, Antonia
Tumino, Rosario
Liu, Geoffrey
Bojesen, Stig E.
Wu, Xifeng
Marchand, Loic Le
Albanes, Demetrius
Bickeböller, Heike
Aldrich, Melinda C.
Bush, William S.
Tardón, Adonina
Rennert, Gad
Teare, M. Dawn
Field, John K.
Kiemeney, Lambertus A.
Lazarus, Philip
Haugen, Aage
Lam, Stephen
Schabath, Matthew B.
Andrew, Angeline S.
Bertazzi, Pier Alberto
Pesatori, Angela C.
Christiani, David C.
Caporaso, Neil
Johansson, Mattias
Mckay, James D.
Brennan, Paul
Hung, Rayjean J.
Amos, Christopher I.
Keywords: Càncer de pulmó
Hàbit de fumar
Lung cancer
Issue Date: 1-Mar-2018
Publisher: Oxford University Press
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 x 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 x 10(-7) and 1.37 with 3.49 x 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 x 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.
Note: Versió postprint del document publicat a:
It is part of: Carcinogenesis, 2018, vol. 39, num. 3, p. 336-346
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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