The German Uranium Miners’ Biobank—A Biobank for OMICs Radiation Research

Systematic bio- and databanks are key prerequisites for modern radiation research to investigate radiation response mechanisms in the context of genetic, environmental and lifestyle-associated factors. This report presents the current status of the German Uranium Miners’ Biobank. In 2008, the bio- and databank was established at the Federal Office for Radiation Protection, and the sampling of biological materials from former uranium miners with and without lung cancer was initiated. For this purpose, various biological specimens, such as DNA and RNA, were isolated from blood samples as well as from formalin-fixed paraffin-embedded lung tissue. High-quality biomaterials suitable for OMICs research and the associated data on occupational radiation and dust exposure, and medical and lifestyle data from over 1000 individuals have been stored so far. Various experimental data, e.g., genome-wide SNPs, whole genome transcriptomic and miRNA data, as well as individual chromosomal aberration data from subgroups of biobank samples, are already available upon request for in-depth research on radiation-induced long-term effects, individual radiation susceptibility to lung cancer and radon-induced fingerprints in lung cancer. This biobank is the first systematic uranium miners´ biobank worldwide that is suitable for OMICs research on radiation-exposed workers. It offers the opportunity to link radiation-induced perturbations of biological pathways or processes and putative adverse outcome(s) by OMICs profiling at different biological organization levels.

Quantitative Proteomics Analysis of Differentially Expressed Proteins in Serum of Former Uranium Miners by Isobaric Tags for the Relative and Absolute Quantitation

The carcinogenicity of radon has been convincingly documented through epidemiological studies of underground miners. However, there is a lack of early warning indicators for radon radiation damage. In this study, mixed serum samples of 3 groups were collected from 27 underground uranium miners and seven aboveground miners according to the radiation exposure dose. The differentially expressed proteins in the serum were identified using the isobaric tags for the relative and absolute quantitation (iTRAQ)-based method. Some differentially expressed proteins were validated by enzyme-linked immunosorbent assay (ELISA) in 84 underground and 32 aboveground miners. A total of 25 co-differentially expressed proteins in 2 underground miner groups were screened, of which 9 were downregulated and 13 were upregulated. Biological process analysis of these proteins using Metascape showed that 5 GO terms were enriched, such as negative regulation of very-low-density lipoprotein particle clearance, endocytosis, and regulated exocytosis. The results of the ELISA for the expression levels of GCN1, CIP2A, and IGHV1-24 in the serum of 116 miners’ serum showed that the levels of GCN1 and CIP2A were consistent with the iTRAQ results. In conclusion, APOC1, APOC2, APOC3, ORM1, ORM2, ANTXR1, GCN1, and CIP2A may be potential early markers of radon radiation damage.

Lung and extrathoracic cancer incidence among underground uranium miners exposed to radon progeny in the Příbram region of the Czech Republic: a case–cohort study

ObjectivesRadon is carcinogenic, but more studies are needed to understand relationships with lung cancer and extrathoracic cancers at low exposures. There are few studies evaluating associations with cancer incidence or assessing the modifying effects of smoking.MethodsWe conducted a case–cohort study with 16 434 underground uranium miners in the Czech Republic with cancer incidence follow-up 1977–1996. Associations between radon exposure and lung cancer, and extrathoracic cancer, were estimated with linear excess relative rate (ERR) models. We examined potential modifying effects of smoking, time since exposure and exposure rate.ResultsUnder a simple ERR model, assuming a 5-year exposure lag, the estimated ERR of lung cancer per 100 working level months (WLM) was 0.54 (95% CI 0.33 to 0.83) and the estimated ERR of extrathoracic cancer per 100 WLM was 0.07 (95% CI −0.17 to 0.72). Most lung cancer cases were observed among smokers (82%), and the estimated ERR of lung cancer per 100 WLM was larger among smokers (ERR/100 WLM=1.35; 95% CI 0.84 to 2.15) than among never smokers (ERR/100 WLM=0.12; 95% CI −0.05 to 0.49). Among smokers, the estimated ERR of lung cancer per 100 WLM decreased with time since exposure from 3.07 (95% CI −0.04 to 10.32) in the period 5–14 years after exposure to 1.05 (95% CI 0.49 to 1.87) in the period 25+ years after exposure.ConclusionsWe observed positive associations between cumulative radon exposure and lung cancer, consistent with prior studies. We observed a positive association between cumulative radon exposure and extrathoracic cancers, although the estimates were small. There was evidence that the association between radon and lung cancer was modified by smoking in a multiplicative or super-multiplicative fashion.

The milk – cheese cycle with alpha emitters – pulmonary contribution to the refeeding of the hormonal system in unoptimal conditions

There is a material truth behind the expression “French people are cheese-eating surrendering monkeys” that involves the higher natural radioactivity in France (averaged) in comparison with the USA, the United Kingdom, Spain and Poland. This comes from the hormone loss related to internal alpha emitting nanoparticulate contamination and involves a compensation with among other things milk drinking and cheese eating. The basic hormone loss can be related to the “surrendering” reputation entirely (testosterone for instance was shown to be destroyed in uranium miners). A secondary cycle emerges to re-establish the sexual difference, where women in these regions typically drink fresh milk whereas men typically eat cheeses that have stayed long in caves and where the hormones have disappeared. This is globally spontaneous. Inhalation of cheese odors serve for cerebral confirmation that hormones have disappeared. That general theorem is a subpart of what was already denominated earlier the meat-pollution cycle for reasons of desire to adopt an easily memorizable name, due to the essentiality of the concept for humankind.

Mortality among uranium miners in North America and Europe: the Pooled Uranium Miners Analysis (PUMA)

Background The Pooled Uranium Miners Analysis (PUMA) study draws together information from cohorts of uranium miners from Canada, the Czech Republic, France, Germany and the USA. Methods Vital status and cause of death were ascertained and compared with expectations based upon national mortality rates by computing standardized mortality ratios (SMRs) overall and by categories of time since first hire, calendar period of first employment and duration of employment as a miner. Results There were 51 787 deaths observed among 118 329 male miners [SMR = 1.05; 95% confidence interval (CI): 1.04, 1.06]. The SMR was elevated for all cancers (n = 16 633, SMR = 1.23; 95% CI: 1.21, 1.25), due primarily to excess mortality from cancers of the lung (n = 7756, SMR = 1.90; 95% CI: 1.86, 1.94), liver and gallbladder (n = 549, SMR = 1.15; 95% CI: 1.06, 1.25), larynx (n = 229, SMR = 1.10; 95% CI: 0.97, 1.26), stomach (n = 1058, SMR = 1.08; 95% CI: 1.02, 1.15) and pleura (n = 39, SMR = 1.06; 95% CI: 0.75, 1.44). Lung-cancer SMRs increased with duration of employment, decreased with calendar period and persisted with time since first hire. Among non-malignant causes, the SMR was elevated for external causes (n = 3362, SMR = 1.41; 95% CI: 1.36, 1.46) and respiratory diseases (n = 4508, SMR = 1.32; 95% CI: 1.28, 1.36), most notably silicosis (n = 814, SMR = 13.56; 95% CI: 12.64, 14.52), but not chronic obstructive pulmonary disease (n = 1729, SMR = 0.98; 95% CI: 0.93, 1.02). Conclusions Whereas there are important obstacles to the ability to detect adverse effects of occupational exposures via SMR analyses, PUMA provides evidence of excess mortality among uranium miners due to a range of categories of cause of death. The persistent elevation of SMRs with time since first hire as a uranium miner underscores the importance of long-term follow-up of these workers.

A discussion on the potential impact of residential radon exposure on the quality of exposure and risk assessment for former uranium miners

Epidemiological evidence of lung cancer risk from radon is based mainly on studies of underground miners where occupational exposures were, historically, relatively high in comparison to residential indoor exposure. However, radiation protection measures have caused radon levels in uranium mines to decrease significantly in more recent periods. Miners’ occupational exposure is limited to their working years while they are exposed to environmental radon at home over their entire lifetime. Even during their limited working years, workers spend much more time at home than in workplaces. The biological effect of radon in mines cannot be distinguished from the biological effect of residential radon. Therefore, for an exposure–risk relationship study of former uranium miners, excess radon-induced lung cancer cases should be related to the combined radon exposure cumulated in workplaces and at homes in excess of the radon exposure of the reference population. This is especially important when residential radon levels differ or vary significantly between miners and the reference population over the course of extended follow-up years. This paper reviews some recent studies on former uranium miners, shares what seems controversial to the author and wonders whether lifetime exposure at home to widely varying radon concentrations can actually impact the quality of exposure assessment, and hence impact the results of the exposure–risk relationship.