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Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development.
Li, Yafang; Xiao, Xiangjun; Bossé, Yohan; Gorlova, Olga; Gorlov, Ivan; Han, Younghun; Byun, Jinyoung; 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; Han, Jiali; Siminovitch, Katherine; 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; Artigas, María Soler; Grankvist, Kjell; Johansson, Mikael; Shepherd, Frances A; Marcus, Michael W; Brunnström, Hans; Manjer, Jonas; Melander, Olle; Muller, David C.
Afiliação
  • Li Y; Baylor College of Medicine, Houston, TX, USA.
  • Xiao X; Baylor College of Medicine, Houston, TX, USA.
  • Bossé Y; Laval University, Quebec, QC, Canada.
  • Gorlova O; Department of Biomedical Data Science, Dartmouth College, Hanover, NH, USA.
  • Gorlov I; Department of Biomedical Data Science, Dartmouth College, Hanover, NH, USA.
  • Han Y; Baylor College of Medicine, Houston, TX, USA.
  • Byun J; Baylor College of Medicine, Houston, TX, USA.
  • Leighl N; University Health Network, The Princess Margaret Cancer Centre, Toronto, CA, USA.
  • Johansen JS; Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
  • Barnett M; Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Chen C; Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Goodman G; Swedish Medical Group, Seattle, WA, USA.
  • Cox A; Department of Oncology, University of Sheffield, Sheffield, UK.
  • Taylor F; Department of Oncology, University of Sheffield, Sheffield, UK.
  • Woll P; Department of Oncology, University of Sheffield, Sheffield, UK.
  • Wichmann HE; Research Unit of Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
  • Manz J; Research Unit of Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
  • Muley T; Thoraxklinik at University Hospital Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Heidelberg, Germany.
  • Risch A; Translational Lung Research Center Heidelberg (TLRC-H), Heidelberg, Germany.
  • Rosenberger A; German Center for Lung Research (DKFZ), Heidelberg, Germany.
  • Han J; University of Salzburg and Cancer Cluster, Salzburg, Austria.
  • Siminovitch K; Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
  • Arnold SM; Indiana University, Bloomington, IN, USA.
  • Haura EB; University of Toronto, Toronto, ON, Canada.
  • Bolca C; University of Kentucky, Markey Cancer Center, Lexington, KY, USA.
  • Holcatova I; Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
  • Janout V; Institute of Pneumology "Marius Nasta", Bucharest, Romania.
  • Kontic M; Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
  • Lissowska J; Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
  • Mukeria A; Clinical Center of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia.
  • Ognjanovic S; M. Sklodowska-Curie Cancer Center, Institute of Oncology, Warsaw, Poland.
  • Orlowski TM; Department of Epidemiology and Prevention, N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation.
  • Scelo G; International Organization for Cancer Prevention and Research, Belgrade, Serbia.
  • Swiatkowska B; Department of Surgery, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland.
  • Zaridze D; International Agency for Research on Cancer, World Health Organization, Lyon, France.
  • Bakke P; Nofer Institute of Occupational Medicine, Department of Environmental Epidemiology, Lodz, Poland.
  • Skaug V; Department of Epidemiology and Prevention, N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation.
  • Zienolddiny S; Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Duell EJ; National Institute of Occupational Health, Oslo, Norway.
  • Butler LM; National Institute of Occupational Health, Oslo, Norway.
  • Houlston R; Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
  • Artigas MS; University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
  • Grankvist K; The Institute of Cancer Research, London, UK.
  • Johansson M; Department of Health Sciences, Genetic Epidemiology Group, University of Leicester, Leicester, UK.
  • Shepherd FA; National Institute for Health Research (NIHR) Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
  • Marcus MW; Department of Medical Biosciences, Umeå University, Umeå, Sweden.
  • Brunnström H; Department of Radiation Sciences, Umeå University, Umeå, Sweden.
  • Manjer J; Princess Margaret Cancer Centre, Toronto, ON, Canada.
  • Melander O; Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
  • Muller DC; Department of Pathology, Lund University, Lund, Sweden.
Oncotarget ; 10(19): 1760-1774, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30956756
ABSTRACT
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 RGL1RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHITTSPAN8 (OR=1.82, p value=7.62x10-11 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.
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Revista: Oncotarget Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: Estados Unidos

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Revista: Oncotarget Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: Estados Unidos