System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Epublish

PubMed: 42947277 DOI: 10.1186/s41021-026-00365-z

Gene-radon interaction effects on lung cancer risk: validation of susceptibility loci using archived DNA from German Uranium miners.

Genes Environ 48(1)

Authors: Albert Rosenberger, Irina Bonzheim, Falko Fend, Beate Hochstrat, Georg Johnen, Alexander Brik, Peter Rozynek, Heike Bickeböller, Simone Mörtl, Maria Gomolka

Affiliations

  • Department of Genetic Epidemiology, University Medical Center, Georg-August- University Göttingen, Göttingen, Germany.
  • Institute of Pathology and Neuropathology, University Hospital Tuebingen and Comprehensive Cancer Center South West, Tübingen, Germany.
  • Section Radiation Epidemiology, Federal Office for Radiation Protection, Oberschleißheim, Germany.
  • Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany.
  • Department of Genetic Epidemiology, University Medical Center, Georg-August- University Göttingen, Göttingen, Germany.
  • Section Radiation Biology, Federal Office for Radiation Protection, Oberschleißheim, Germany.

Abstract

BACKGROUND

Radon exposure increases lung cancer risk, shown in studies on indoor exposure (low exposure) and uranium miners (high exposure). Genome-wide and candidate gene studies have identified DNA variants that interact with occupational radon to modify lung cancer risk.

METHOD

Highly fragmented DNA samples of 611 individuals were genotyped using next-generation sequencing. DNA variant associations could be assessed in 526 out of 611 WISMUT uranium miners with lung cancer. The relative risk of lung cancer per allele (marginal effect) as well as its dependence on radon exposure (gene-environment (GxE) interaction) could be estimated from the enrichment of one allele compared to the distribution of genotypes expected under the HWE assumption (Hardy-Weinberg equilibrium). Exposure to gamma radiation, long-lived radionuclides, fine dust, silicate dust and arsenic was considered in the same way.

RESULTS

For markers from six (UBE2U, CDKN2A, SIRT1, NAV2, ST8SIA2, TP53) of the 10 genes examined, a significant modification of the genetic relative risk for lung cancer due to mining-specific radon exposure [in WLM] was observed.

CONCLUSION

Radon exposure may be the main cause of some of the observed GxE interactions involving UBE2U, CDKN2A and SIRT1, but it may not be the only one. This conclusion is supported by the function of these genes, as based on relevant literature. For another marker of the gene SOX5, a GxE interaction can presumably be attributed to exposure to arsenic. For the remaining genes, no single environmental factor (radon, dust or arsenic) can unambiguously be identified as sole cause of the GxE interaction.

CLINICAL TRIAL NUMBER

Not applicable.

MeSH

Dust, Genes, Lung, Neoplasms, Lung Neoplasms, Alleles, Environment