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Verfasst von:Rosenberger, Albert [VerfasserIn]   i
 Risch, Angela [VerfasserIn]   i
 Muley, Thomas [VerfasserIn]   i
Titel:Genetic modifiers of radon-induced lung cancer risk
Titelzusatz:a genome-wide interaction study in former uranium miners
Verf.angabe:Albert Rosenberger, Rayjean J. Hung, David C. Christiani, Neil E. Caporaso, Geoffrey Liu, Stig E. Bojesen, Loic Le Marchand, Ch. A. Haiman, Demetrios Albanes, Melinda C. Aldrich, Adonina Tardon, G. Fernández-Tardón, Gad Rennert, John K. Field, B. Kiemeney, Philip Lazarus, Aage Haugen, Shanbeh Zienolddiny, Stephen Lam, Matthew B. Schabath, Angeline S. Andrew, Hans Brunnsstöm, Gary E. Goodman, Jennifer A. Doherty, Chu Chen, M. Dawn Teare, H.-Erich Wichmann, Judith Manz, Angela Risch, Thomas R. Muley, Mikael Johansson, Paul Brennan, Maria Teresa Landi, Christopher I. Amos, Beate Pesch, Georg Johnen, Thomas Brüning, Heike Bickeböller, Maria Gomolka
E-Jahr:2018
Jahr:3 July 2018
Umfang:14 S.
Fussnoten:Gesehen am 12.04.2019
Titel Quelle:Enthalten in: International archives of occupational and environmental health
Ort Quelle:Berlin : Springer, 1930
Jahr Quelle:2018
Band/Heft Quelle:91(2018), 8, Seite 937-950
ISSN Quelle:1432-1246
Abstract:PurposeRadon 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.MethodsSamples 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.ResultsWe 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.ConclusionThe 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.
DOI:doi:10.1007/s00420-018-1334-3
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1007/s00420-018-1334-3
 DOI: https://doi.org/10.1007/s00420-018-1334-3
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:DNA repair
 Gene-environment interaction
 GWAS
 Occupational exposure
 Radon progeny
K10plus-PPN:166320487X
Verknüpfungen:→ Zeitschrift

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