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Gene–gene interacti...
Gene–gene interaction of AhR with and within the Wnt cascade affects susceptibility to lung cancer
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- Rosenberger, Albert (författare)
- Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany; Institut Für Genetische Epidemiologie, Universitätsmedizin Göttingen, Humboldtallee 32, Göttingen, Germany
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- Muttray, Nils (författare)
- Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany
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- Hung, Rayjean J. (författare)
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, University of Toronto, ON, Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
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- Christiani, David C. (författare)
- Department of Environmental Health, Harvard T.H. Chan School of Public Health and Massachusetts General Hospital/Harvard Medical School, MA, Boston, United States
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- Caporaso, Neil E. (författare)
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, MD, Bethesda, United States
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- Liu, Geoffrey (författare)
- Medical Oncology and Medical Biophysics, Princess Margaret Cancer Centre, ON, Toronto, Canada; Medicine and Epidemiology, Dalla Lana School of Public Health, University of Toronto, ON, Toronto, Canada
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- Bojesen, Stig E. (författare)
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen, Denmark
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- Le Marchand, Loic (författare)
- Epidemiology Program, University of Hawaii Cancer Center, HI, Honolulu, United States
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- Albanes, Demetrios (författare)
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, MD, Bethesda, United States
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- Aldrich, Melinda C. (författare)
- Department of Thoracic Surgery, Division of Epidemiology, Vanderbilt University Medical Center, TN, Nashville, United States
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- Tardon, Adonina (författare)
- Faculty of Medicine, University of Oviedo, ISPA and CIBERESP, Oviedo, Spain
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- Fernández-Tardón, Guillermo (författare)
- Faculty of Medicine, University of Oviedo, ISPA and CIBERESP, Oviedo, Spain
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- Rennert, Gad (författare)
- Clalit National Cancer Control Center at Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel
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- Field, John K. (författare)
- Department of Molecular and Clinical Cancer Medicine, Roy Castle Lung Cancer Research Programme, The University of Liverpool, Liverpool, United Kingdom
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- Davies, Michael P. A. (författare)
- Department of Molecular and Clinical Cancer Medicine, Roy Castle Lung Cancer Research Programme, The University of Liverpool, Liverpool, United Kingdom
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- Liloglou, Triantafillos (författare)
- Department of Molecular and Clinical Cancer Medicine, Roy Castle Lung Cancer Research Programme, The University of Liverpool, Liverpool, United Kingdom
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- Kiemeney, Lambertus A. (författare)
- Departments of Health Evidence and Urology, Radboud University Medical Center, Nijmegen, Netherlands
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- Lazarus, Philip (författare)
- Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, WA, Spokane, United States
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- Wendel, Bernadette (författare)
- Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany
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- Haugen, Aage (författare)
- National Institute of Occupational Health, Oslo, Norway
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- Zienolddiny, Shanbeh (författare)
- National Institute of Occupational Health, Oslo, Norway
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- Lam, Stephen (författare)
- British Columbia Cancer Agency, BC, Vancouver, Canada
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- Schabath, Matthew B. (författare)
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, FL, Tampa, United States
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- Andrew, Angeline S. (författare)
- Department of Epidemiology, Geisel School of Medicine, NH, Hanover, United States
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- Duell, Eric J. (författare)
- Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
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- Arnold, Susanne M. (författare)
- Markey Cancer Center, University of Kentucky, KY, Lexington, United States
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- Goodman, Gary E. (författare)
- Swedish Medical Group, WA, Seattle, United States
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- Chen, Chu (författare)
- Program in Epidemiology, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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- Doherty, Jennifer A. (författare)
- Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, UT, Salt Lake City, United States
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- Taylor, Fiona (författare)
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom
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- Cox, Angela (författare)
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom
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- Woll, Penella J. (författare)
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom
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- Risch, Angela (författare)
- University of Salzburg and Cancer Cluster Salzburg, Salzburg, Austria
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- Muley, Thomas R. (författare)
- Member of the German Center for Lung Research (DZL), Translational Lung Research Center (TLRC) Heidelberg, Heidelberg, Germany; Translational Research Unit, Thoraxklinik, University Hospital Heidelberg, Heidelberg, Germany
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- Johansson, Mikael (författare)
- Umeå universitet,Onkologi
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- Brennan, Paul (författare)
- International Agency for Research on Cancer, World Health Organization, Lyon, France
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- Landi, Maria Teresa (författare)
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, MD, Bethesda, United States
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- Shete, Sanjay S. (författare)
- Department of Biostatistics, Division of Basic Sciences, The University of Texas MD Anderson Cancer Center, TX, Houston, United States
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- Amos, Christopher I. (författare)
- Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, TX, Houston, United States
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- Bickeböller, Heike (författare)
- Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany
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(creator_code:org_t)
- 2022-01-31
- 2022
- Engelska.
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Ingår i: European Journal of Medical Research. - : BioMed Central (BMC). - 0949-2321 .- 2047-783X. ; 27:1
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://eurjmedres.b...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: Aberrant Wnt signalling, regulating cell development and stemness, influences the development of many cancer types. The Aryl hydrocarbon receptor (AhR) mediates tumorigenesis of environmental pollutants. Complex interaction patterns of genes assigned to AhR/Wnt-signalling were recently associated with lung cancer susceptibility.Aim: To assess the association and predictive ability of AhR/Wnt-genes with lung cancer in cases and controls of European descent.Methods: Odds ratios (OR) were estimated for genomic variants assigned to the Wnt agonist and the antagonistic genes DKK2, DKK3, DKK4, FRZB, SFRP4 and Axin2. Logistic regression models with variable selection were trained, validated and tested to predict lung cancer, at which other previously identified SNPs that have been robustly associated with lung cancer risk could also enter the model. Furthermore, decision trees were created to investigate variant × variant interaction. All analyses were performed for overall lung cancer and for subgroups.Results: No genome-wide significant association of AhR/Wnt-genes with overall lung cancer was observed, but within the subgroups of ever smokers (e.g., maker rs2722278 SFRP4; OR = 1.20; 95% CI 1.13–1.27; p = 5.6 × 10–10) and never smokers (e.g., maker rs1133683 Axin2; OR = 1.27; 95% CI 1.19–1.35; p = 1.0 × 10–12). Although predictability is poor, AhR/Wnt-variants are unexpectedly overrepresented in optimized prediction scores for overall lung cancer and for small cell lung cancer. Remarkably, the score for never-smokers contained solely two AhR/Wnt-variants. The optimal decision tree for never smokers consists of 7 AhR/Wnt-variants and only two lung cancer variants.Conclusions: The role of variants belonging to Wnt/AhR-pathways in lung cancer susceptibility may be underrated in main-effects association analysis. Complex interaction patterns in individuals of European descent have moderate predictive capacity for lung cancer or subgroups thereof, especially in never smokers.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Association
- Decision trees
- Gene–gene integration
- Never smoker
- Polygenic risk score
- Prediction
- Small cell lung cancer
- Susceptibility
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- ref (ämneskategori)
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Rosenberger, Alb ...
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Muttray, Nils
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Hung, Rayjean J.
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Christiani, Davi ...
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Caporaso, Neil E ...
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Liu, Geoffrey
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visa fler...
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Bojesen, Stig E.
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Le Marchand, Loi ...
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Albanes, Demetri ...
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Aldrich, Melinda ...
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Tardon, Adonina
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Fernández-Tardón ...
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Rennert, Gad
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Field, John K.
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Davies, Michael ...
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Liloglou, Triant ...
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Kiemeney, Lamber ...
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Lazarus, Philip
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Wendel, Bernadet ...
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Haugen, Aage
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Zienolddiny, Sha ...
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Lam, Stephen
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Schabath, Matthe ...
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Andrew, Angeline ...
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Duell, Eric J.
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Arnold, Susanne ...
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Goodman, Gary E.
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Chen, Chu
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Doherty, Jennife ...
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Taylor, Fiona
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Cox, Angela
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Woll, Penella J.
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Risch, Angela
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Muley, Thomas R.
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Johansson, Mikae ...
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Brennan, Paul
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Landi, Maria Ter ...
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Shete, Sanjay S.
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Amos, Christophe ...
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Bickeböller, Hei ...
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