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Genetic modifiers o...
Genetic modifiers of radon-induced lung cancer risk : a genome-wide interaction study in former uranium miners
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- Rosenberger, Albert (författare)
- University Medical Center Göttingen
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- Hung, Rayjean J. (författare)
- University of Toronto
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- Christiani, David C. (författare)
- Massachusetts General Hospital,Harvard T.H. Chan School of Public Health,Fred Hutchinson Cancer Research Center
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- Caporaso, Neil E. (författare)
- National Cancer Institute, USA
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- Liu, Geoffrey (författare)
- University of Toronto
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- Bojesen, Stig E. (författare)
- Gentofte Hospital,University of Copenhagen
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- Le Marchand, Loic (författare)
- University of Hawaii at Manoa
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- Haiman, C. A. (författare)
- University of Southern California
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- Albanes, Demetrios (författare)
- National Cancer Institute, USA
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- Aldrich, Melinda C. (författare)
- Vanderbilt University
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- Tardon, Adonina (författare)
- University of Oviedo,CIBER Epidemiology and Public Health (CIBERESP)
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- Fernández-Tardón, G. (författare)
- University of Oviedo,CIBER Epidemiology and Public Health (CIBERESP)
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- Rennert, Gad (författare)
- Carmel Medical Center
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- Field, John K. (författare)
- University of Liverpool
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- Kiemeney, B. (författare)
- Radboud University Nijmegen
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- Lazarus, Philip (författare)
- Washington State University College of Pharmacy
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- Haugen, Aage (författare)
- National Institute of Occupational Health, Norway
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- Zienolddiny, Shanbeh (författare)
- National Institute of Occupational Health, Norway
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- Lam, Stephen (författare)
- British Columbia Cancer Agency
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- Schabath, Matthew B. (författare)
- H. Lee Moffitt Cancer Center & Research Institute
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- Andrew, Angeline S. (författare)
- Dartmouth College
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- Brunnsstöm, Hans (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Institutionen för laboratoriemedicin,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Department of Laboratory Medicine
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- Goodman, Gary E. (författare)
- Swedish Medical Center
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- Doherty, Jennifer A. (författare)
- University of Utah,Fred Hutchinson Cancer Research Center
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- Chen, Chu (författare)
- Fred Hutchinson Cancer Research Center
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- Teare, M. Dawn (författare)
- University of Sheffield
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- Wichmann, H. E. (författare)
- Ludwig-Maximilian University of Munich,Technical University of Munich,Helmholtz Zentrum München
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- Manz, Judith (författare)
- Helmholtz Zentrum München
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- Risch, Angela (författare)
- University of Salzburg,University Hospital Heidelberg
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- Muley, Thomas R. (författare)
- University Hospital Heidelberg
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- Johansson, Mikael (författare)
- Umeå universitet,Umeå University,Onkologi
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- Brennan, Paul (författare)
- International Agency for Research on Cancer, World Health Organization
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- Landi, Maria Teresa (författare)
- National Cancer Institute, USA
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- Amos, Christopher I. (författare)
- Dartmouth College
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- Pesch, Beate (författare)
- Ruhr-University Bochum
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- Johnen, Georg (författare)
- Ruhr-University Bochum
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- Brüning, Thomas (författare)
- Ruhr-University Bochum
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- Bickeböller, Heike (författare)
- University Medical Center Göttingen
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- Gomolka, Maria (författare)
- Federal Office for Radiation Protection
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(creator_code:org_t)
- 2018-07-03
- 2018
- Engelska.
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 91:8, s. 937-950
- Relaterad länk:
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http://dx.doi.org/10...
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https://europepmc.or...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Purpose: Radon is a risk factor for lung cancer and uranium miners are more exposed than the general population. A genome-wide interaction analysis was carried out to identify genomic loci, genes or gene sets that modify the susceptibility to lung cancer given occupational exposure to the radioactive gas radon. Methods: Samples from 28 studies provided by the International Lung Cancer Consortium were pooled with samples of former uranium miners collected by the German Federal Office of Radiation Protection. In total, 15,077 cases and 13,522 controls, all of European ancestries, comprising 463 uranium miners were compared. The DNA of all participants was genotyped with the OncoArray. We fitted single-marker and in multi-marker models and performed an exploratory gene-set analysis to detect cumulative enrichment of significance in sets of genes. Results: We discovered a genome-wide significant interaction of the marker rs12440014 within the gene CHRNB4 (OR = 0.26, 95% CI 0.11–0.60, p = 0.0386 corrected for multiple testing). At least suggestive significant interaction of linkage disequilibrium blocks was observed at the chromosomal regions 18q21.23 (p = 1.2 × 10−6), 5q23.2 (p = 2.5 × 10−6), 1q21.3 (p = 3.2 × 10−6), 10p13 (p = 1.3 × 10−5) and 12p12.1 (p = 7.1 × 10−5). Genes belonging to the Gene Ontology term “DNA dealkylation involved in DNA repair” (GO:0006307; p = 0.0139) or the gene family HGNC:476 “microRNAs” (p = 0.0159) were enriched with LD-blockwise significance. Conclusion: The well-established association of the genomic region 15q25 to lung cancer might be influenced by exposure to radon among uranium miners. Furthermore, lung cancer susceptibility is related to the functional capability of DNA damage signaling via ubiquitination processes and repair of radiation-induced double-strand breaks by the single-strand annealing mechanism.
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 -- Hälsovetenskap -- Arbetsmedicin och miljömedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Occupational Health and Environmental Health (hsv//eng)
Nyckelord
- DNA repair
- Gene–environment interaction
- GWAS
- Occupational exposure
- Radon progeny
- GWAS
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- art (ämneskategori)
- ref (ämneskategori)
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Rosenberger, Alb ...
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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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Bojesen, Stig E.
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visa fler...
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Le Marchand, Loi ...
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Haiman, C. A.
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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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Kiemeney, B.
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Lazarus, Philip
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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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Brunnsstöm, Hans
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Goodman, Gary E.
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Doherty, Jennife ...
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Chen, Chu
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Teare, M. Dawn
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Wichmann, H. E.
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Manz, Judith
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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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Amos, Christophe ...
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Pesch, Beate
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Johnen, Georg
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Brüning, Thomas
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Bickeböller, Hei ...
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Gomolka, Maria
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