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  • Rosenberger, AlbertUniversity Medical Center Göttingen (author)

Genetic modifiers of radon-induced lung cancer risk : a genome-wide interaction study in former uranium miners

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018-07-03
  • Springer Science and Business Media LLC,2018

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:f2a23017-f207-4870-a320-34e9558ef91a
  • https://lup.lub.lu.se/record/f2a23017-f207-4870-a320-34e9558ef91aURI
  • https://doi.org/10.1007/s00420-018-1334-3DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-155783URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Hung, Rayjean J.University of Toronto (author)
  • Christiani, David C.Harvard T.H. Chan School of Public Health,Massachusetts General Hospital,Fred Hutchinson Cancer Research Center (author)
  • Caporaso, Neil E.National Cancer Institute, USA (author)
  • Liu, GeoffreyUniversity of Toronto (author)
  • Bojesen, Stig E.Gentofte Hospital,University of Copenhagen (author)
  • Le Marchand, LoicUniversity of Hawaii at Manoa (author)
  • Haiman, C. A.University of Southern California (author)
  • Albanes, DemetriosNational Cancer Institute, USA (author)
  • Aldrich, Melinda C.Vanderbilt University (author)
  • Tardon, AdoninaCIBER Epidemiology and Public Health (CIBERESP),University of Oviedo (author)
  • Fernández-Tardón, G.University of Oviedo,CIBER Epidemiology and Public Health (CIBERESP) (author)
  • Rennert, GadCarmel Medical Center (author)
  • Field, John K.University of Liverpool (author)
  • Kiemeney, B.Radboud University Nijmegen (author)
  • Lazarus, PhilipWashington State University College of Pharmacy (author)
  • Haugen, AageNational Institute of Occupational Health, Norway (author)
  • Zienolddiny, ShanbehNational Institute of Occupational Health, Norway (author)
  • Lam, StephenBritish Columbia Cancer Agency (author)
  • Schabath, Matthew B.H. Lee Moffitt Cancer Center & Research Institute (author)
  • Andrew, Angeline S.Dartmouth College (author)
  • Brunnsstöm, HansLund 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(Swepub:lu)med-hsb (author)
  • Goodman, Gary E.Swedish Medical Center (author)
  • Doherty, Jennifer A.University of Utah,Fred Hutchinson Cancer Research Center (author)
  • Chen, ChuFred Hutchinson Cancer Research Center (author)
  • Teare, M. DawnUniversity of Sheffield (author)
  • Wichmann, H. E.Ludwig-Maximilian University of Munich,Technical University of Munich,Helmholtz Zentrum München (author)
  • Manz, JudithHelmholtz Zentrum München (author)
  • Risch, AngelaUniversity of Salzburg,University Hospital Heidelberg (author)
  • Muley, Thomas R.University Hospital Heidelberg (author)
  • Johansson, MikaelUmeå universitet,Umeå University,Onkologi(Swepub:umu)mijo0025 (author)
  • Brennan, PaulInternational Agency for Research on Cancer, World Health Organization (author)
  • Landi, Maria TeresaNational Cancer Institute, USA (author)
  • Amos, Christopher I.Dartmouth College (author)
  • Pesch, BeateRuhr-University Bochum (author)
  • Johnen, GeorgRuhr-University Bochum (author)
  • Brüning, ThomasRuhr-University Bochum (author)
  • Bickeböller, HeikeUniversity Medical Center Göttingen (author)
  • Gomolka, MariaFederal Office for Radiation Protection (author)
  • University Medical Center GöttingenUniversity of Toronto (creator_code:org_t)

Related titles

  • In:International Archives of Occupational and Environmental Health: Springer Science and Business Media LLC91:8, s. 937-9500340-01311432-1246

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