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

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 Europe...

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Vydané v:	Carcinogenesis (New York) Ročník 39; číslo 3; s. 336
Hlavní autori:	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, Demetrios, Bickeböller, Heike, Aldrich, Melinda C, Bush, William S, Tardon, 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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	England 08.03.2018
Predmet:	Carcinoma, Non-Small-Cell Lung - etiology Carcinoma, Non-Small-Cell Lung - genetics Case-Control Studies Gene-Environment Interaction Genetic Predisposition to Disease - genetics Genome-Wide Association Study Genotype Humans Lung Neoplasms - etiology Lung Neoplasms - genetics Polymorphism, Single Nucleotide Smoking - adverse effects White People
ISSN:	1460-2180, 1460-2180
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Popis
Shrnutí:	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 13336 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13970 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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1460-2180 1460-2180
DOI:	10.1093/carcin/bgx113