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The debate surrounding possible adverse health effects from the civil use of nuclear power under normal operating conditions has been on-going since its introduction. It was particularly intensified by the detection of three leukaemia clusters near nuclear installations, i.e. near the reprocessing plants in Sellafield and Dounreay, UK, and near the Krümmel nuclear power plant, Germany, the last of which commenced between 1990 and 1991 and was first described in 1992; it continued until 2003, and an elevated risk up to 2005 has been reported in the literature. A number of expert commissions and working groups were set up by the governments of the German federal states of Lower Saxony and Schleswig-Holstein to investigate the possible causes of the cluster. An overview of the many risk factors that were investigated as a possible explanation of the Krümmel cluster is given here, focussing on radiation, but also including other risk factors. Further, results from related epidemiological and cytogenetic studies are described. In summary, the cause of the occurrence of the Krümmel cluster has to be considered as unknown. Further research on the causes of childhood leukaemia is needed, focussing on epigenetics and on gene-environment interaction. An update of the leukaemia incidence around the Krümmel site shows that the incidence rates are now comparable to the average rate in Germany.

Direct quantitative assessment of health risks following exposure to ionizing radiation is based on findings from epidemiological studies. Populations affected by nuclear bomb testing are among those that allow such assessment. The population living around the former Soviet Union’s Semipalatinsk nuclear test site is one of the largest human cohorts exposed to radiation from nuclear weapons tests. Following research that started in the 1960s, a registry that contains information on more than 300,000 individuals residing in the areas neighboring to the test site was established. Four nuclear weapons tests, conducted from 1949 to 1956, resulted in non-negligible radiation exposures to the public, corresponding up to approximately 300 mGy external dose. The registry contains relevant information about those who lived at the time of the testing as well as about their offspring, including biological material. An international group of scientists worked together within the research project SEMI-NUC funded by the European Union, and concluded that the registry provides a novel, mostly unexplored, and valuable resource for the assessment of the population risks associated with environmental radiation exposure. Suggestions for future studies and pathways on how to use the best dose assessment strategies have also been described in the project. Moreover, the registry could be used for research on other relevant public health topics.

The Wismut cohort is currently the largest single study on the health risks associated with occupational exposures to ionising radiation and dust accrued during activities related to uranium mining. The cohort has ∼59 000 male workers, first employed between 1946 and 1989, at the Wismut Company in Germany. The main effect is a statistically significant increase in mortality from lung cancer with both increasing cumulative radon exposure and silica dust exposure. Risks for cancers of the extrathoracic airways, all extra-pulmonary cancers and cardiovascular diseases associated with radiation exposures have been evaluated. Cohort mortality rates for some other cancer sites, stomach and liver, are statistically significantly increased in relation to the general population, but not statistically significantly related to occupational exposures. No associations between leukaemia mortality and occupational doses of ionising radiation were found.

International audience; Recent findings related to childhood leukaemia incidence near nuclear installations have raised questions which can be answered neither by current knowledge on radiation risk nor by other established risk factors. In 2012, a workshop was organised on this topic with two objectives (a) review of results and discussion of methodological limitations of studies near nuclear installations; (b) identification of directions for future research into the causes and pathogenesis of childhood leukaemia. The workshop gathered 42 participants from different disciplines, extending widely outside of the radiation protection field. Regarding the proximity of nuclear installations, the need for continuous surveillance of childhood leukaemia incidence was highlighted, including a better characterisation of the local population. The creation of collaborative working groups was recommended for consistency in methodologies and the possibility of combining data for future analyses. Regarding the causes of childhood leukaemia, major fields of research were discussed (environmental risk factors, genetics, infections, immunity, stem cells, experimental research). The need for multidisciplinary collaboration in developing research activities was underlined, including the prevalence of potential predisposition markers and investigating further the infectious aetiology hypothesis. Animal studies and genetic/epigenetic approaches appear of great interest. Routes for future research were pointed out. © 2014 IOP Publishing Ltd.

Uranium mining occurred between 1946 and 1990 at the former Wismut mining company in East Germany. 58,987 male former employees form the largest single uranium miners cohort, which has been followed up for causes of mortality occurring from the beginning of 1946 to the end of 2003. The purpose of this paper is to present the radon exposure related cancer mortality risk based on 20,920 deaths, 2 million person-years, and 6,373 cancers. The latter include 3,016 lung cancers and 3,053 extrapulmonary solid cancers. Internal Poisson regression was used to estimate the excess relative risk (ERR) per unit of cumulative radon exposure in Working Level Months (WLM) for all major sites and for the follow-up period from 1946 to 2003. The simple cohort ERR WLM for lung cancer is 0.20% [95% confidence interval (CI): 0.17%; 0.22%]. The ERR model for lung cancer is linear in radon exposure with exponential effect modifiers that depend on age at median exposure, time since median exposure, and radon exposure-rate. In this model the central estimate of ERR WLM is 1.06% (95% CI: 0.69%; 1.42%) for an age at median exposure of 33 y, a time since median exposure of 11 y, and an exposure-rate of 2.7 WL. This central ERR decreases by 5% for each unit exposure-rate increase. The ERR decreases by 32% with each decade increase in age at median exposure and also decreases by 54% with each decade increase in time since median exposure. The ERR WLM for all extrapulmonary solid cancers combined without effect modification is 0.014% (95% CI: 0.006%; 0.023%). The ERR model for extrapulmonary solid cancer is linear in radon exposure with an exponential effect modifier which depends on age-attained. In this model the central estimate of ERR WLM is 0.040% (95% CI: -0.001%; 0.082%) for an age-attained of 44. The ERR decreases by 37% with each decade increase in age-attained. The highest ERR WLM, after lung, is observed for cancers of the pharynx (0.16%), tongue/mouth (0.045%), and liver (0.04%).

The nuclear bomb testing conducted at the Semipalatinsk nuclear test site in Kazakhstan is of great importance for today’s radiation protection research, particularly in the area of low dose exposures. This type of radiation is of particular interest due to the lack of research in this field and how it impacts population health. In order to understand the possible health effects of nuclear bomb testing, it is important to determine what studies have been conducted on the effects of low dose exposure and dosimetry, and evaluate new epidemiologic data and biological material collected from populations living in proximity to the test site. With time, new epidemiological data has been made available, and it is possible that these data may be linked to biological samples. Next to linking existing and newly available data to examine health effects, the existing dosimetry system needs to be expanded and further developed to include residential areas, which have not yet been taken into account. The aim of this paper is to provide an overview of previous studies evaluating the health effects of nuclear testing, including some information on dosimetry efforts, and pointing out directions for future epidemiologic studies.

An increased risk of cardiovascular diseases after exposure to low doses of ionizing radiation has been suggested among the atomic bomb survivors. Few and inconclusive results on this issue are available from miner studies. A positive correlation between coronary heart disease mortality and radon exposure has been reported in the Newfoundland fluorspar miners study, yet low statistical power due to small sample size was of concern. To get further insight into this controversial issue, data from the German uranium miners cohort study were used, which is by far the largest miner study up to date. The cohort includes 59,001 male subjects who were employed for at least six months between 1946 and 1989 at the former Wismut uranium company in Eastern Germany. Exposure to radon, long-lived radionuclides and external gamma radiation was estimated by using a detailed job-exposure matrix. About 16,598 cohort members were deceased until 31 December 1998, including 5,417 deaths from cardiovascular diseases. Linear Poisson regression models were used to estimate the excess relative risk (ERR) per unit of cumulative radiation exposure after adjusting for attained age and calendar period. No trend in risk of circulatory diseases with increasing cumulative exposure to either radon [ERR per 100 working level month: 0.0006; 95% confidence limit (CI): -0.004 to 0.006], external gamma radiation (ERR per Sv: -0.26, 95% CI: -0.6 to 0.05) or long-lived radionuclides (ERR per 100 kBqh/m3: -0.2, 95% CI: -0.5 to 0.06), respectively, was observed. This was also true for the sub-group heart disease and stroke. Our findings do not support an association between cardiovascular disease mortality and exposure to radiation among miners, yet low doses and uncontrolled confounding hamper interpretation.

Since the early 1990s, information on radiation-exposed populations other than those exposed from the Chernobyl accident in 1986 has become increasingly available for international scientific research. It is essential to understand how the cohorts of exposed populations have been defined and what mechanisms can be used to study their health outcomes. Different international scientific research collaborations currently investigate four population groups chronically exposed to ionizing radiation during the late 1940s and early 1950s in the Russian Federation and in Kazakhstan. In this framework, collaborations have been established to develop cause-of-death registers in each of these four areas for future mortality follow-up purposes with the aim of studying the health effects of ionizing radiation. The emphasis of this effort is on assessing the information sources available, the mechanisms of data collection and coding, and the data quality and completeness of the information collected. One of the major challenges is the harmonization of all these aspects between the four different centers to the extent possible, taking into account that much of the actual data has been collected over many decades.

A registry of the rural population in the Altai region exposed to fallout from nuclear tests at the Semipalatinsk test site (STS) was established more than four decades after the first Soviet nuclear explosion on August 29, 1949. Information about individuals living in an exposed and a control area was collected using all available local sources, such as kolkhoz documentation, school registries, medical treatment records and interviews with residents. As a result, a database comprising an exposed group of 39 179 individuals from 53 Altai region villages, 6769 external and 3303 internal controls was compiled. For several settlements, effective dose estimates reached the level of 1.5 Sv, while the average effective dose estimate in the exposed group was 340 mSv. Dosimetric data, vital status information and health records gathered at rayon and village medical facilities are held in the registry. Cause-of-death information for deceased residents is obtained from death registration forms archived at the Altai region vital statistics office. At present, a follow-up of approximately 40% of the population exposed in 1949 has been done. More will be added by searching for migrants to the larger towns of the Altai region, i.e. Barnaul, Rubtsovsk and Biisk. In order to assess the influence of radiation exposure, analytical studies with a case-control design for stomach and lung cancer are currently being prepared. The number of known cases is sufficient to detect an odds ratio of 1.5 at the 95% confidence level. Epidemiological studies in populations affected by fallout from STS may be equally important to the atomic bomb survivors' study for the direct quantification of radiation effects. The range of exposure rates experienced will extend the acute high-dose-rate findings from Hiroshima/Nagasaki towards acute and protracted lower exposures, which are more relevant for radiation protection issues.

A combined analysis of three case-control studies nested in three European uranium miner cohorts was performed to study the joint effects of radon exposure and smoking on lung cancer death risk. Occupational history and exposure data were available from the cohorts. Smoking information was reconstructed using self-administered questionnaires and occupational medical archives. Linear excess relative risk models adjusted for smoking were used to estimate the lung cancer risk associated with radon exposure. The study includes 1046 lung cancer cases and 2492 controls with detailed radon exposure data and smoking status. The ERR/WLM adjusted for smoking is equal to 0.008 (95% CI: 0.0040.014). Time since exposure is shown to be a major modifier of the relationship between radon exposure and lung cancer risk. Fitting geometric mixture models yielded arguments in favor of a sub-multiplicative interaction between radon and smoking. This combined study is the largest case-control study to investigate the joint effects of radon and smoking on lung cancer risk among miners. The results confirm that the lung carcinogenic effect of radon persists even when smoking is adjusted for, with arguments in favor of a sub-multiplicative interaction between radon and smoking. © 2011 by Radiation Research Society.

The data on risk of mortality from cardiovascular disease due to radiation exposure at low or medium doses are inconsistent. This paper reports an analysis of the Semipalatinsk historical cohort exposed to radioactive fallout from nuclear testing in the vicinity of the Semipalatinsk Nuclear Test Site, Kazakhstan. The cohort study, which includes 19,545 persons of exposed and comparison villages in the Semipalatinsk region, had been set up in the 1960s and comprises 582,656 person-years of follow-up between 1960 and 1999. A dosimetric approach developed by the U.S. National Cancer Institute (NCI) has been used. Radiation dose estimates in this cohort range from 0 to 630 mGy (whole-body external). Overall, the exposed population showed a high mortality from cardiovascular disease. Rates of mortality from cardiovascular disease in the exposed group substantially exceeded those of the comparison group. Dose-response analyses were conducted for both the entire cohort and the exposed group only. A dose-response relationship that was found when analyzing the entire cohort could be explained completely by differences between the baseline rates in exposed and unexposed groups. When taking this difference into account, no statistically significant dose-response relationship for all cardiovascular disease, for heart disease, or for stroke was found. Our results suggest that within this population and at the level of doses estimated, there is no detectable risk of radiation-related mortality from cardiovascular disease.

The possible confounding effect of smoking on radon-associated risk for lung cancer mortality was investigated in a case-control study nested in the cohort of German uranium miners. The study included 704 miners who died of lung cancer and 1,398 controls matched individually for birth year and attained age. Smoking status was reconstructed from questionnaires and records from the mining company's health archives for 421 cases and 620 controls. Data on radon exposure were taken from a job-exposure matrix. Smoking adjusted odds ratios for lung cancer in relation to cumulative radon exposure have been calculated with conditional logistic regression. The increase in risk per Working Level Month (WLM) was assessed with a linear excess relative risk (ERR) model taking smoking into account as a multiplicative factor. In addition, the potential impact of temporal factors on the ERR per WLM was examined. Lung cancer mortality risk increased with increasing radon exposure, yielding a crude ERR per WLM of 0.25% (95% CI: 0.13-0.46%). Adjustment for smoking led only to marginal changes of the radon-associated lung cancer risks. The adjusted ERR per WLM was very similar (0.23%, 95%-CI: 0.11-0.46%) to the crude risk and to the risk found in the Wismut cohort study. This stability of the radon-related lung cancer risks with and without adjustment for smoking suggests that smoking does not act as a major confounder in this study and presumably also not in the cohort study.

Epidemiological evidence of lung cancer risk from radon is known since the early 1960s, when first studies on uranium miners were published. The risk was modeled in terms of relative risk in dependence on cumulated exposure. Since then, follow-up of studies has been extended, which allowed the analysis of modifying factors such as time since exposure (TSE), age at exposure (AE), attained age, and exposure rate. The present analysis was conducted in the frame of the Alpha-Risk European research program and aimed at estimating the lung cancer risk associated to radon exposure among miners with low levels of exposure and good quality of exposure assessment. The large numbers of miners included in the joint study allow a simultaneous analysis of modifying effects using exposure windows, which are appropriate in studies with protracted exposures. The analysis is based on three European cohort studies of uranium miners: Czech, French and German, including 9979, 5086 and 35084 miners, respectively. By the end of follow-up, 921, 159, and 458 lung cancer deaths were observed in these cohorts, respectively. The excess relative risks per working level month (ERR/WLM) for the three studies were 0.0116 (95%CI 0.0076-0.0157), 0.0061 (95%CI 0.0018-0.0105), and 0.0043 (95%CI 0.0028-0.0057), respectively. The different estimates are caused mainly by the so-called inverse effect of exposure rate and by quality of exposure, which both are correlated with time since exposure. We evaluated simultaneously the effects of TSE in 3 windows (5-19 years before, 20-34, 35+) and of AE in 3 windows (-29 years, 30-39, 40+). The analysis showed a strong decrease of the ERR/WLM with TSE (28% in period 20-34 years and 11% after 35 years in comparison to window 5-19). The simultaneous effect of AE was also significant: ERR/WLM for AE more than 40 years was 53% of that for AE below 30). These results will permit to improve our knowledge on the long-term risks associated to radon exposure. The present work was supported by the European Commission (Contract FI6R 516483).

KEYWORDS CLASSIFICATION: Arsenic;Biotransformation;cancer epidemiology;chemically induced;epidemiology;Environmental Exposure;Epidemiology,Molecular;Evaluation;genetics;Germany;Humans;Inhalation;metabolism;methods;Neoplasms;Occupational Exposure;Radiation Protection;toxicity. Arsenic, one of the most significant hazards in the environment affecting millions of people around the world, is associated with several diseases including cancers of skin, lung, urinary bladder, kidney and liver. Groundwater contamination by arsenic is the main route of exposure. Inhalation of airborne arsenic or arsenic-contaminated dust is a common health problem in many ore mines. This review deals with the questions raised in the epidemiological studies such as the dose-response relationship, putative confounders and synergistic effects, and methods evaluating arsenic exposure. Furthermore, it describes the metabolic pathways of arsenic, and its biological modes of action. The role of arsenic in the development of cancer is elucidated in the context of combined epidemiological and biological studies. However, further analyses by means of molecular epidemiology are needed to improve the understanding of cancer aetiology induced by arsenic.

Little information is available on the health effects of exposures to fallout from Soviet nuclear weapons testing and on the combined external and internal environmental exposures that have resulted from these tests. This paper reports the first analysis of the Semipalatinsk historical cohort exposed in the vicinity of the Semipalatinsk nuclear test site, Kazakhstan. The cohort study, which includes 19,545 inhabitants of exposed and comparison villages of the Semipalatinsk region, was set up in the 1960s and comprises 582,750 person-years of follow-up between 1960 and 1999. Cumulative effective radiation dose estimates in this cohort range from 20 mSv to approximately 4 Sv. Rates of mortality and cancer mortality in the exposed group substantially exceeded those of the comparison group. Dose-response analyses within the exposed group confirmed a significant trend with dose for all solid cancers (P0.0001) and for digestive and respiratory cancers (P = 0.0255 and P0.0001), whereas no consistent dose-response trend was found for all causes of death (P = 0.4296). Regarding specific cancer sites, a significant trend with dose was observed for lung cancer (P = 0.0001), stomach cancer (P = 0.0050), and female breast cancer (P = 0.0040) as well as for esophagus cancer in women (P = 0.0030). The excess relative risk per sievert for all solid cancers combined was 1.77 (1.35; 2.27) based on the total cohort data, yet a selection bias regarding the comparison group could not be entirely ruled out. The excess relative risk per sievert based on the cohort's exposed group was 0.81 (0.46; 1.33) for all solid cancers combined and thus still exceeds current risk estimates from the Life Span Study. Future epidemiological assessments based on this cohort will benefit from extension of follow-up and ongoing validation of dosimetric data.

We briefly outline existing information about several cohorts in the Southern Urals, Semipalatinsk and the Altai regions, in addition to those discussed in the companion papers in this issue of Radiation and Environmental Biophysics. These include: (a) the East-Urals Radiation Trace (EURT) cohort of individuals (exposed to fallout from the September 1957 explosion of a storage tank containing liquid radioactive waste from the Mayak Production Association ) as well as their offspring, (b) the cohort of exposed parents (i.e. workers of the Mayak facility) and their children, having been established with the aim of examining reproductive health, and (c) several additional cohorts in the Altai region and in Semipalatinsk, where investment of additional resources would greatly facilitate the progress of ongoing studies. Furthermore, we include a brief description of the Russian Human Radiobiology Tissue Repository, which has been established in the city of Ozyorsk and is in the process of making an inventory of autopsied tissues from 700 deceased Mayak workers and of collecting and storing donations of blood and tumor tissues from the members of the Mayak workers cohort currently residing in the city.

A temporary increase in the incidence of infant leukaemia in Greece was reported by Petridou et al., which was attributed to in utero exposure to ionising radiation resulting from the Chernobyl accident. We performed a similar analysis based on the data of the German Childhood Cancer Registry in order to check whether the observation could be confirmed by means of independent data. Applying the same definitions as Petridou et al., we also observed an increased incidence of infant leukaemia in a cohort of children born after the Chernobyl accident. More detailed analyses, regarding areas with different contamination levels and dose rate gradients over time after the accident, showed, however, no clear trend with regard to exposure. It would therefore appear less likely that the observed effect was caused by exposure to ionising radiation due to the Chernobyl accident.

Occupational studies of aircrew in civil or military aviation did not receive much attention until the beginning of this decade. Since 1990, a number of epidemiological studies has been published on the cancer risk among flight personnel. Their results are equivocal: elevated cancer risks have been observed in some studies, but not in others. The exposure situation for pilots and flight attendants is unique with respect to several factors and particularly in that cosmic rays contribute substantially to their cumulative radiation dose. The average annual doses received are relatively low, however, and commonly range between 3 and 6 mSv. Results of epidemiological studies are presented as well as information on planned studies.

This study considers whether or not exposure to radioactive fallout from the Chernobyl accident led to an increased prevalence of congenital malformations in infants born in Bavaria, the German state with the highest levels of contamination after the accident. The odds ratios for major malformations after the accident relative to before were used as indicators for adverse health effects. Since measurements of caesium in soil showed that contamination was considerably higher in Southern Bavaria than in Northern Bavaria, the odds ratios were calculated for both regions separately. Analysis did not show a significant increase in any of the odds ratios of the selected malformations in Southern Bavaria as compared to Northern Bavaria. Consequently, this study provides no evidence that radiation from Chernobyl caused an increase in the birth prevalence of major congenital malformations.

In Germany, the largest single cohort study on uranium miners to date is being conducted. The cohort includes about 64,000 workers of the former Wismut company in eastern Germany. Inclusion criteria were: a date of employment between 1946 and 1989, a minimum period of employment of 180 days, and complete information on working history. Due to poor working conditions in the late 1940s and early 1950s, miners were exposed to high levels of radiation, while later radiation exposure was significantly reduced. The aim of the cohort study is to evaluate the risk of lung cancer and other cancers associated with several indicators of exposure to radon and its progeny, with particular attention to low levels of radiation. Radon exposure will be estimated by a detailed job- exposure matrix. Some information about smoking, dust and arsenic is already available. About 49,000 miners are defined as exposed (underground or processing), while the internal control group (surface only) consists of 15,000 workers. A total of 1,436 lung cancer deaths among cohort members have been reported. The first mortality follow-up will be finished early in 2002, and a total of about 3,000 lung cancer deaths are expected by then.