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Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development
Y. Li, X. Xiao, Y. Bossé, O. Gorlova, I. Gorlov, Y. Han, J. Byun, N. Leighl, JS. Johansen, M. Barnett, C. Chen, G. Goodman, A. Cox, F. Taylor, P. Woll, HE. Wichmann, J. Manz, T. Muley, A. Risch, A. Rosenberger, J. Han, K. Siminovitch, SM. Arnold,...
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
Grantová podpora
001
World Health Organization - International
P30 CA076292
NCI NIH HHS - United States
P50 CA119997
NCI NIH HHS - United States
R35 CA197449
NCI NIH HHS - United States
NLK
Free Medical Journals
od 2010
Freely Accessible Journals
od 2010
PubMed Central
od 2010
Europe PubMed Central
od 2010
Open Access Digital Library
od 2010-01-01
- Publikační typ
- časopisecké články MeSH
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.
Baylor College of Medicine Houston TX USA
Biomedical Data Science Department Dartmouth College Hanover NH USA
British Columbia Cancer Agency Vancouver Canada
Clinical Center of Serbia School of Medicine University of Belgrade Belgrade Serbia
Department of Biomedical Data Science Dartmouth College Hanover NH USA
Department of Cancer Epidemiology H Lee Moffitt Cancer Center and Research Institute Tampa FL USA
Department of Clinical Science University of Bergen Bergen Norway
Department of Clinical Sciences and Community Health University of Milan Milan Italy
Department of Epidemiology Geisel School of Medicine Hanover NH USA
Department of Epidemiology The University of Texas MD Anderson Cancer Center Houston TX USA
Department of Medical Biosciences Umeå University Umeå Sweden
Department of Oncology University of Sheffield Sheffield UK
Department of Pathology Lund University Lund Sweden
Department of Pharmaceutical Sciences College of Pharmacy Washington State University Spokane WA USA
Department of Radiation Sciences Umeå University Umeå Sweden
Department of Surgery National Tuberculosis and Lung Diseases Research Institute Warsaw Poland
Department of Thoracic Oncology H Lee Moffitt Cancer Center and Research Institute Tampa FL USA
Epidemiology Program University of Hawaii Cancer Center Honolulu HI USA
Faculty of Medicine Lund University Lund Sweden
Faculty of Medicine University of Ostrava Ostrava Czech Republic
Fred Hutchinson Cancer Research Center Seattle WA USA
Hellenic Health Foundation Athens Greece
Indiana University Bloomington IN USA
Institute of Pneumology Marius Nasta Bucharest Romania
Institute of Translational Medicine University of Liverpool Liverpool UK
International Agency for Research on Cancer World Health Organization Lyon France
International Organization for Cancer Prevention and Research Belgrade Serbia
IUOPA University of Oviedo and CIBERESP Faculty of Medicine Campus del Cristo s n Oviedo Spain
Laval University Quebec QC Canada
Lunenfeld Tanenbaum Research Institute of Mount Sinai Hospital University of Toronto Toronto Canada
M Sklodowska Curie Cancer Center Institute of Oncology Warsaw Poland
Molecular and Nutritional Epidemiology Unit CSPO Scientific Institute of Tuscany Florence Italy
National Institute of Occupational Health Oslo Norway
Nofer Institute of Occupational Medicine Department of Environmental Epidemiology Lodz Poland
Princess Margaret Cancer Centre Toronto ON Canada
Radboud University Medical Center Nijmegen The Netherlands
School of Health and Related Research University of Sheffield Sheffield UK
School of Public Health St Mary's Campus Imperial College London London UK
Section for Epidemiology Department of Public Health Aarhus University Aarhus Denmark
Swedish Medical Group Seattle WA USA
The Institute of Cancer Research London UK
Unit of Nutrition and Cancer Catalan Institute of Oncology Barcelona Spain
University Health Network The Princess Margaret Cancer Centre Toronto CA USA
University of Kentucky Markey Cancer Center Lexington KY USA
Citace poskytuje Crossref.org
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