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  • 1. Hung, Rayjean J.
    et al.
    Spitz, Margaret R.
    Houlston, Richard S.
    Schwartz, Ann G.
    Field, John K.
    Ying, Jun
    Li, Yafang
    Han, Younghun
    Ji, Xuemei
    Chen, Wei
    Wu, Xifeng
    Gorlov, Ivan P.
    Na, Jie
    de Andrade, Mariza
    Liu, Geoffrey
    Brhane, Yonathan
    Diao, Nancy
    Wenzlaff, Angela
    Davies, Michael P. A.
    Liloglou, Triantafillos
    Timofeeva, Maria
    Muley, Thomas
    Rennert, Hedy
    Saliba, Walid
    Ryan, Brid M.
    Bowman, Elise
    Barros-Dios, Juan-Miguel
    Perez-Rios, Monica
    Morgenstern, Hal
    Zienolddiny, Shanbeh
    Skaug, Vidar
    Ugolini, Donatella
    Bonassi, Stefano
    van der Heijden, Erik H. F. M.
    Tardon, Adonina
    Bojesen, Stig E.
    Landi, Maria Teresa
    Johansson, Mattias
    Bickeboeller, Heike
    Arnold, Susanne
    Le Marchand, Loic
    Melander, Olle
    Andrew, Angeline
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Caporaso, Neil
    Teare, M. Dawn
    Schabath, Matthew B.
    Aldrich, Melinda C.
    Kiemeney, Lambertus A.
    Wichmann, H-Erich
    Lazarus, Philip
    Mayordomo, Jose
    Neri, Monica
    Haugen, Aage
    Zhang, Zuo-Feng
    Ruano-Ravina, Alberto
    Brenner, Hermann
    Harris, Curtis C.
    Orlow, Irene
    Rennert, Gadi
    Risch, Angela
    Brennan, Paul
    Christiani, David C.
    Amos, Christopher I.
    Yang, Ping
    Gorlova, Olga Y.
    Lung Cancer Risk in Never-Smokers of European Descent is Associated With Genetic Variation in the 5(p)15.33 TERT-CLPTM1Ll Region2019In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 14, no 8, p. 1360-1369Article in journal (Refereed)
    Abstract [en]

    Introduction: Inherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer. Methods: We conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer. Results: We detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722-0.820; p value 5.31 x 10(-16)), rs380286 (OR: 0.770, 95% CI: 0.723-0.820; p value 4.32 x 10(-16)), and rs4975616 OR: 0.778, 95% CI: 0.730-0.829; p value 1.04 x 10(-14)). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate. Conclusions: We found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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