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Li, Y.* ; Xiao, X.* ; Bossé, Y.* ; Gorlova, O.* ; Gorlov, I.* ; Han, Y.* ; Byun, J.* ; Leighl, N.* ; Johansen, J.S.* ; Barnett, M.* ; Chen, C.* ; Goodman, G.* ; Cox, A.* ; Taylor, F.* ; Woll, P.* ; Wichmann, H.-E. ; Manz, J. ; Muley, T.* ; Risch, A.* ; Rosenberger, A.* ; Han, J.* ; Siminovitch, K.* ; Arnold, S.M.* ; Haura, E.B.* ; Bolca, C.* ; Holcatova, I.* ; Janout, V.* ; Kontic, M.* ; Lissowska, J.* ; Mukeria, A.* ; Ognjanovic, S.* ; Orlowski, T.M.* ; Scelo, G.* ; Swiatkowska, B.* ; Zaridze, D.* ; Bakke, P.* ; Skaug, V.* ; Zienolddiny, S.* ; Duell, E.J.* ; Butler, L.M.* ; Houlston, R.* ; Artigas, M.S.* ; Grankvist, K.* ; Johansson, M.* ; Shepherd, F.A.* ; Marcus, M.W.* ; Brunnström, H.* ; Manjer, J.* ; Melander, O.* ; Müller, D.C.* ; Overvad, K.* ; Trichopoulou, A.* ; Tumino, R.* ; Liu, G.* ; Bojesen, S.E.* ; Wu, X.* ; Le Marchand, L.* ; Albanes, D.* ; Bickeböller, H.* ; Aldrich, M.C.* ; Bush, W.S.* ; Tardón, A.* ; Rennert, G.* ; Dawn Teare, M.* ; Field, J.K.* ; Kiemeney, L.A.* ; Lazarus, P.* ; Haugen, A.* ; Lam, S.* ; Schabath, M.B.* ; Andrew, A.S.* ; Bertazzi, P.A.* ; Pesatori, A.C.* ; Christiani, D.C.* ; Caporaso, N.* ; McKay, J.D.* ; Brennan, P.* ; Hung, R.J.* ; Amos, C.I.*

Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development.

Oncotarget 10, 1760-1774 (2019)
Verlagsversion Forschungsdaten DOI
Creative Commons Lizenzvertrag
The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in (OR=0.44, value=3.27x10 in overall lung cancer and OR=0.41, value=9.71x10 in non-small cell lung cancer), (OR=0.73, value=1.01x10 in adenocarcinoma) and (OR=1.82, value=7.62x10 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Epistasis ; Functional Annotation ; Lung Cancer ; Oncogenesis
ISSN (print) / ISBN 1949-2553
e-ISSN 1949-2553
Zeitschrift OncoTarget
Quellenangaben Band: 10, Heft: 19, Seiten: 1760-1774 Artikelnummer: , Supplement: ,
Verlag Impact Journals LLC
Begutachtungsstatus Peer reviewed