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Autor
Albanes, Demetrios 1 Aldrich, Melinda C 1 Amos, Christopher I 1 Andrew, Angeline S 1 Arnold, Susanne M 1 Artigas, María Soler 1 Bakke, Per 1 Barnett, Matt 1 Bertazzi, Pier Alberto 1 Bickeböller, Heike 1 Bojesen, Stig E 1 Bolca, Ciprian 1 Bossé, Yohan 1 Brennan, Paul 1 Brunnström, Hans 1 Bush, William S 1 Butler, Lesley M 1 Byun, Jinyoung 1 Caporaso, Neil 1 Chen, Chu 1
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Pracoviště
Baylor College of Medicine Houston TX... 1 Biomedical Data Science Department Da... 1 British Columbia Cancer Agency Vancou... 1 Clalit National Cancer Control Center... 1 Clinical Center of Serbia School of M... 1 Department of Biomedical Data Science... 1 Department of Cancer Epidemiology H L... 1 Department of Clinical Biochemistry H... 1 Department of Clinical Science Univer... 1 Department of Clinical Sciences and C... 1 Department of Epidemiology Geisel Sch... 1 Department of Epidemiology Program in... 1 Department of Epidemiology The Univer... 1 Department of Epidemiology and Biosta... 1 Department of Epidemiology and Preven... 1 Department of Genetic Epidemiology Un... 1 Department of Health Sciences Genetic... 1 Department of Medical Biosciences Ume... 1 Department of Oncology Herlev and Gen... 1 Department of Oncology University of ... 1
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Autor
Albanes, Demetrios 1 Aldrich, Melinda C 1 Amos, Christopher I 1 Andrew, Angeline S 1 Arnold, Susanne M 1 Artigas, María Soler 1 Bakke, Per 1 Barnett, Matt 1 Bertazzi, Pier Alberto 1 Bickeböller, Heike 1 Bojesen, Stig E 1 Bolca, Ciprian 1 Bossé, Yohan 1 Brennan, Paul 1 Brunnström, Hans 1 Bush, William S 1 Butler, Lesley M 1 Byun, Jinyoung 1 Caporaso, Neil 1 Chen, Chu 1
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Pracoviště
Baylor College of Medicine Houston TX... 1 Biomedical Data Science Department Da... 1 British Columbia Cancer Agency Vancou... 1 Clalit National Cancer Control Center... 1 Clinical Center of Serbia School of M... 1 Department of Biomedical Data Science... 1 Department of Cancer Epidemiology H L... 1 Department of Clinical Biochemistry H... 1 Department of Clinical Science Univer... 1 Department of Clinical Sciences and C... 1 Department of Epidemiology Geisel Sch... 1 Department of Epidemiology Program in... 1 Department of Epidemiology The Univer... 1 Department of Epidemiology and Biosta... 1 Department of Epidemiology and Preven... 1 Department of Genetic Epidemiology Un... 1 Department of Health Sciences Genetic... 1 Department of Medical Biosciences Ume... 1 Department of Oncology Herlev and Gen... 1 Department of Oncology University of ... 1
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PubMed Central od 2010
Europe PubMed Central od 2010
Open Access Digital Library od 2010-01-01
PubMed
30956756
DOI
10.18632/oncotarget.26678
Knihovny.cz E-zdroje
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 RGL1:RAD51B (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), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (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.
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