| Title |
Genetic modifiers of radon-induced lung cancer risk: a genome-wide interaction study in former uranium miners
|
|---|---|
| Published in |
International Archives of Occupational and Environmental Health, July 2018
|
| DOI | 10.1007/s00420-018-1334-3 |
| Pubmed ID | |
| Authors |
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 |
| Abstract |
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. 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. 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. 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. |
X Demographics
The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 43% |
| United Kingdom | 1 | 14% |
| Unknown | 3 | 43% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 6 | 86% |
| Scientists | 1 | 14% |
Mendeley readers
The data shown below were compiled from readership statistics for 61 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 61 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 12 | 20% |
| Student > Bachelor | 8 | 13% |
| Professor | 7 | 11% |
| Student > Doctoral Student | 6 | 10% |
| Student > Postgraduate | 3 | 5% |
| Other | 13 | 21% |
| Unknown | 12 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 16 | 26% |
| Computer Science | 4 | 7% |
| Nursing and Health Professions | 3 | 5% |
| Agricultural and Biological Sciences | 3 | 5% |
| Biochemistry, Genetics and Molecular Biology | 3 | 5% |
| Other | 13 | 21% |
| Unknown | 19 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 November 2019.
All research outputs
#7,325,024
of 23,815,455 outputs
Outputs from International Archives of Occupational and Environmental Health
#753
of 1,988 outputs
Outputs of similar age
#122,442
of 329,304 outputs
Outputs of similar age from International Archives of Occupational and Environmental Health
#10
of 21 outputs
Altmetric has tracked 23,815,455 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 1,988 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.5. This one has gotten more attention than average, scoring higher than 58% of its peers.
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We're also able to compare this research output to 21 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.