Radioepidemiology in the aftermath of the nuclear program of the former Soviet Union: Unique lessons to be learnt

  The military and civilian nuclear activities in the former Soviet Union led to unique exposures and resulted in high cumulative doses in several populations. In comparison to the atomic bomb survivors, at present the most important cohort in radiation epidemiology, collective and individual doses received by early workers in the plutonium production facilities at Mayak (Chelyabinsk), Techa River residents downstream of Mayak, populations downwind of the Semipalatinsk test site, and subpopulations of Chernobyl victims surpass the Hiroshima/Nagasaki experience in most cases. Even more importantly, the dose rates cover the full range of exposures relevant for radiation protection, i.e., acute to year-long chronic exposures from environmental contamination and bone seeking radionuclides. Parallel to the humanitarian need to mitigate health effects from these exposures, the unique opportunities for research on radiation risks related to low dose rate and chronic radiation have to be explored. Increased efforts by the global radiation research community are needed to address the many questions which cannot be answered by the acutely irradiated survivors of Hiroshima/Nagasaki. Specific attention needs to be drawn to the validation of available exposure and health records and to dose reconstruction which must include dietary sources of exposure. Preliminary intercomparison and validation exercises indicate potentially large sources of error, e.g., due to uncertainties in the reconstruction of early exposures and effects and due to continuing incorporation. Received: 29 February 1996 / Accepted in revised form: 6 March 1996     

Ischemic Heart Disease in Workers at Mayak PA: Latency of Incidence Risk after Radiation Exposure

We present an updated analysis of incidence and mortality from atherosclerotic induced ischemic heart diseases in the cohort of workers at the Mayak Production Association (PA). This cohort constitutes one of the most important sources for the assessment of radiation risk. It is exceptional because it comprises information on several other risk factors. While most of the workers have been exposed to external gamma radiation, a large proportion has additionally been exposed to internal radiation from inhaled plutonium. Compared to a previous study by Azizova et al. 2012, the updated dosimetry system MWDS-2008 has been applied and methods of analysis have been revised. We extend the analysis of the significant incidence risk and observe that main detrimental effects of external radiation exposure occur after more than about 30 years. For mortality, significant risk was found in males with an excess relative risk per dose of 0.09 (95% CI: 0.02; 0.16) while risk was insignificant for females. With respect to internal radiation exposure no association to risk could be established.     

Radiation Effects on Mortality from Solid Cancers Other than Lung,Liver, and Bone Cancer in the Mayak Worker Cohort: 1948–2008

Radiation effects on mortality from solid cancers other than lung, liver, and bone cancer in the Mayak worker cohort: 1948–2008. The cohort of Mayak Production Association (PA) workers in Russia offers a unique opportunity to study the effects of prolonged low dose rate external gamma exposures and exposure to plutonium in a working age population. We examined radiation effects on the risk of mortality from solid cancers excluding sites of primary plutonium deposition (lung, liver, and bone surface) among 25,757 workers who were first employed in 1948–1982. During the period 1948–2008, there were 1,825 deaths from cancers other than lung, liver and bone. Using colon dose as a representative external dose, a linear dose response model described the data well. The excess relative risk per Gray for external gamma exposure was 0.16 (95% CI: 0.07 – 0.26) when unadjusted for plutonium exposure and 0.12 (95% CI 0.03 – 0.21) when adjusted for plutonium dose and monitoring status. There was no significant effect modification by sex or attained age. Plutonium exposure was not significantly associated with the group of cancers analyzed after adjusting for monitoring status. Site-specific risks were uncertainly estimated but positive for 13 of the 15 sites evaluated with a statistically significant estimate only for esophageal cancer. Comparison with estimates based on the acute exposures in atomic bomb survivors suggests that the excess relative risk per Gray for prolonged external exposure in Mayak workers may be lower than that for acute exposure but, given the uncertainties, the possibility of equal effects cannot be dismissed.     

Mortality from cardiovascular diseases in the Semipalatinsk historical cohort, 1960-1999, and its relationship to radiation exposure

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.     

A critical survey of fish measurements in populations of the southern Urals

A critical survey of all published measurements made so far aimed at retrospective biological dosimetry using fluorescence in situ hybridisation (FISH) techniques on some workers at the Mayak reprocessing plant and on members of the Techa River cohort is given. Each individual has a recorded dose derived from personal monitoring measurements, usually external gamma-rays for Mayak workers or from reconstruction techniques, usually internally derived for the Techa River cohort. From the person's age, which affects the control level, and the stated dose, an expected number of translocations is calculated for each individual and comparisons made to the observed numbers of translocations. From this, an assessment of how well FISH studies can help to validate existing estimates of dose is made. This varies from study to study. Good agreement is generally obtained for the Techa River cohort and lower doses of the Mayak cohort. Rather poorer agreement applies to the more highly exposed Mayak workers. Some of the discrepancy could be because the FISH painting technique was new and was applied to populations before a proper investigation on how to use it for retrospective biological dosimetry had taken place. In addition, too few cells were generally scored per individual so that statistical uncertainties were large.     

Early leukemia effect during chronic exposure to radiation with high doses

The preliminary results of the analysis of leukemia morbidity in the sub-cohort of workers from PA "Mayak" exposed with high (more than 4Gy) doses during relatively short time range (few years) have been obtained in terms of materials from the medical-dosimetry register (SUrIBPh). The earlier dynamics of the leukemia morbidity implementation (2-5 years after the beginning of exposure) was established for this sub-cohort, in contrast to that predicted on the base of examination of the cohort of atomic bombardment victims from Japan cities (LSS). The "'early" leukemia effect is connected with intensive cell death and has a threshold nature. It could be supposed, that intensification of born-marrow hematopoetics restricts a potential of reparation processes and leads to earlier (in contrast with that observed in the LSS cohort) implementation of carcinogenetic effect. Using propositions developed to describe the process of the creation of consecutive specific stable mutation in the target cells, the options is proposed of multistage model, which allows the prediction of post-radiation dynamics of leukemia morbidity intensity. Both data from LSS(DS86) and from the register for workers from PA "Mayak" were used to asses the model parameters. The satisfactory agreement is illustrated between the observed dynamics of leukemia morbidity and the model calculations.     

Characteristics of the cohort of workers at the Mayak nuclear complex.

At Branch No. 1 of the Russian State Research Center "Biophysics Institute", a registry has been created of workers at the "Mayak" Production Association, the first nuclear complex in Russia. This registry includes 18,830 persons hired at Mayak's nuclear reactors and radiochemical and plutonium production plant between 1948 and 1972. Twenty-five percent of these workers are women. As of December 31, 1994, the vital status is known for approximately 90% of the cohort members. A total of 5,118 persons have died. The cause for 97% of total deaths has been ascertained. The cohort members were exposed to both external gamma radiation and internal radiation from incorporated plutonium. The plutonium body burden has been measured in 30% of the cohort members with potential for plutonium exposure. External gamma-ray doses were in the range from tenths of milligrays to about 10 Gy, and plutonium body burdens were up to about 260 kBq. In view of the nature of the Mayak worker cohort, it has the potential to provide reasonably precise, quantitative estimates of the long-term health effects associated with chronic low-dose-rate exposure to external gamma radiation as well as internal radiation from plutonium. However, a number of issues must be addressed before credible risk estimates can be obtained from this cohort. These issues include the development of an appropriate internal comparison group and/or external rates and separating of the effects of internal and external exposures on risk estimates.     

Cerebrovascular diseases in nuclear workers first employed at the Mayak PA in 1948–1972

Incidence and mortality from cerebrovascular diseases (CVD) (430–438 ICD-9 codes) have been studied in a cohort of 18,763 workers first employed at the Mayak Production Association (Mayak PA) in 1948–1972 and followed up to the end of 2005. Some of the workers were exposed to external gamma-rays only while others were exposed to a mixture of external gamma-rays and internal alpha-particle radiation due to incorporated ²³⁹Pu. After adjusting for non-radiation factors, there were significantly increasing trends in CVD incidence with total absorbed dose from external gamma-rays and total absorbed dose to liver from internal alpha radiation. The CVD incidence was statistically significantly higher among workers with total absorbed external gamma-ray doses greater than 0.20 Gy compared to those exposed to lower doses; the data were consistent with a linear trend in risk with external dose. The CVD incidence was statistically significantly higher among workers with total absorbed internal alpha-radiation doses to liver from incorporated ²³⁹Pu greater than 0.025 Gy compared to those exposed to lower doses. There was no statistically significant trend in CVD mortality risk with either external gamma-ray dose or internal alpha-radiation dose to liver. The risk estimates obtained are generally compatible with those from other large occupational studies, although the incidence data point to higher risk estimates compared to those from the Japanese A-bomb survivors. Further studies of the unique cohort of Mayak workers chronically exposed to external and internal radiation will allow improving the reliability and validating the radiation safety standards for occupational and public exposure.     

Mortality risk of cardiovascular diseases for occupationally exposed workers

Results of the risk analysis of mortality from ischemic heart disease (IHD) in the cohort of Mayak nuclear workers (18763 individuals) first employed in 1948-1972, with follow-up to 31.12.2005, were summarized. The mortality risk of IHD in the cohort of Mayak workers depended on the non-radiation factors such as gender, age, calendar period, smoking, alcohol consumption, arterial hypertension, body mass index. There was no statistically significant relationship between mortality from 1HD and total external dose. The risk of mortality from IHD was significantly higher for workers exposed to the total absorbed dose to liver > 0.025 Gy from internal alpha-radiation. There was a significantly increasing trend (ERR/Gy) of the IHD mortality with the total absorbed dose to liver from internal alpha-radiation due to incorporated plutonium. However, there was a decreasing trend of ERR/Gy with restriction of the follow-up to Ozyorsk and adjustment for the external dose.     

Cerebrovascular Diseases in Workers at Mayak PA: The Difference in Radiation Risk between Incidence and Mortality

A detailed analysis of cerebrovascular diseases (CeVD) for the cohort of workers at Mayak Production Association (PA) is presented. This cohort is especially suitable for the analysis of radiation induced circulatory diseases, due to the detailed medical surveillance and information on several risk factors. The risk after external, typically protracted, gamma exposure is analysed, accounting for potential additional internal alpha exposure. Three different endpoints have been investigated: incidence and mortality from all cerebrovascular diseases and incidence of stroke. Particular emphasis was given to the form of the dose-response relationship and the time dependence of the radiation induced risk. Young attained age was observed to be an important, aggravating modifier of radiation risk for incidence of CeVD and stroke. For incidence of CeVD, our analysis supports a dose response sub-linear for low doses. Finally, the excess relative risk per dose was confirmed to be significantly higher for incidence of CeVD compared to CeVD mortality and incidence of stroke. Arguments are presented for this difference to be based on a true biological effect.     

Lung cancer mortality among male nuclear workers of the Mayak facilities in the former Soviet Union

An analysis of lung cancer mortality in a cohort of 1,669 Mayak workers who started their employment in the plutonium and reprocessing plants between 1948 and 1958 has been carried out in terms of a relative risk model. Particular emphasis has been given to a discrimination of the effects of external gamma-ray exposure and internal alpha-particle exposure due to incorporated plutonium. This study has also used the information from a cohort of 2,172 Mayak reactor workers who were exposed only to external gamma rays. The baseline lung cancer mortality rate has not been taken from national statistics but has been derived from the cohort itself. For both alpha particles and gamma rays, the results of the analysis are consistent with linear dose dependences. The estimated excess relative risk per unit organ dose equivalent in the lung due to the plutonium alpha particles at age 60 equals, according to the present study, 0.6/Sv, with a radiation weighting factor of 20 for alpha particles. The 95% confidence range is 0.39/Sv to 1.0/Sv. For the gamma-ray component, the present analysis suggests an excess relative risk for lung cancer mortality at age 60 of 0.20/Sv, with, however, a large 95% confidence range of-0.04/Sv to 0.69/Sv.     

Mapping of quantitative trait loci controlling adaptive traits in coastal Douglas-fir. IV. Cold-hardiness QTL verification and candidate gene mapping

Quantitative trait locus (QTL) analyses are used by geneticists to characterize the genetic architecture of quantitative traits, provide a foundation for marker-aided-selection (MAS), and provide a framework for positional selection of candidate genes. The most useful QTL for breeding applications are those that have been verified in time, space, and/or genetic background. In this study, spring cold-hardiness of Douglas-fir foliar tissues was evaluated in two clonally replicated (n=170 and 383 clones) full-sib cohorts derived from the same parental cross in two different years (made 5 years apart). The cohorts were established in widely separated forest test sites and tissues were artificially freeze tested using different cold injury assessment methods. Four of six unique QTL detected for spring cold-hardiness in needles of Cohort 1 were tentatively verified in the second cohort. Four additional QTL were detected in Cohort 2, two on linkage groups (LGs) not previously represented in the smaller cohort. In total, 10 unique QTL were identified across both cohorts. Seventeen of twenty-nine putative cold-hardiness candidate genes (Douglas-fir ESTs) placed on the Douglas-fir linkage map locate within the 95% confidence intervals of spring needle cold-hardiness QTL from the two cohorts and thus represent priority targets for initiating association mapping in Douglas-fir.     

Mortality from solid cancers other than lung,liver, and bone in relation to external dose among plutonium and non-plutonium workers in the Mayak Worker Cohort

Exposure to ionizing radiation has well-documented long-term effects on cancer rates and other health outcomes in humans. While in vitro experimental studies had demonstrated that the nature of some radiation effects depend on both total dose of the radiation and the dose rate (i.e., the pattern of dose distribution over time), the question of whether or not the carcinogenic effect of radiation exposure depends on the dose rate remains unanswered. Another issue of interest concerns whether or not concomitant exposure to external gamma rays and inhaled plutonium aerosols has any effect on the external exposure effects. The analyses of the present paper focus on the risk of solid cancers at sites other than lung, liver, and bone in Mayak workers. Recent findings are reviewed indicating that there is no evidence of plutonium dose response for these cancers in the Mayak worker cohort. Then the evidence for differences in the external dose effects among workers with and without the potential for exposure to alpha particles from inhaled plutonium is examined. It is found that there is no evidence that exposure to plutonium aerosols significantly affects the risk associated with external exposure. While the Mayak external dose risk estimate of an excess relative risk of 0.16 per Gy is somewhat lower than an appropriately normalized risk estimate from the Life Span Study of Japanese atomic bomb survivors, the uncertainties in these estimates preclude concluding that the external dose excess relative risks of this group of solid cancers differ in the two cohorts.     

Lung cancer mortality among nuclear workers of the Mayak facilities in the former Soviet Union. An updated analysis considering smoking as the main confounding factor

A new analysis of lung cancer mortality in a cohort of male Mayak workers who started their employment in the plutonium and reprocessing plants between 1948 and 1958 has been carried out in terms of a relative risk model. The follow-up has been extended until 1999, moreover a new dosimetry system (DOSES2000) has been established. Particular emphasis has been given to a discrimination of the effects of external -exposure and internal -exposure due to incorporated plutonium. This study has also utilized and incorporated the information from a cohort of Mayak reactor workers, who were exposed only externally to -rays. The influence of smoking as the main confounding factor for lung cancer has been studied. The baseline lung cancer mortality rate was not taken from national statistics but was derived from the cohort itself. The estimated excess relative risk for the plutonium -rays was 0.23/Sv (95%CI: 0.16–0.31). The resulting risk coefficient for external -ray exposure was very low with a statistically insignificant estimate of 0.058/Sv (95%CI: –0.072–0.20). The inferred relative risk for smokers was 16.5 (95%CI: 12.6–20.5).     

Lung cancer in Mayak workers

The cohort of nuclear workers at the Mayak Production Association, located in the Russian Federation, is a unique resource for providing information on the health effects of exposure to plutonium as well as the effects of protracted external dose. Lung cancer mortality risks were evaluated in 21,790 Mayak workers, a much larger group than included in previous evaluations of lung cancer risks in this cohort. These analyses, which included 655 lung cancer deaths occurring in the period 1955-2000, were the first to evaluate both excess relative risk (ERR) and excess absolute risk (EAR) models and to give detailed attention to the modifying effects of gender, attained age and age at hire. Lung cancer risks were found to be significantly related to both internal dose to the lung from plutonium and external dose, and risks were described adequately by linear functions. For internal dose, the ERR per gray for females was about four times higher than that for males, whereas the EAR for females was less than half that for males; the ERR showed a strong decline with attained age, whereas the EAR increased with attained age until about age 65 and then decreased. Parallel analyses of lung cancer mortality risks in Mayak workers and Japanese A-bomb survivors were also conducted. Efforts currently under way to improve both internal and external dose estimates, and to develop data on smoking, should result in more accurate risk estimates in the future.     

Bone cancers in Mayak workers

Bone cancer mortality risks were evaluated in 11,000 workers who started working at the "Mayak" Production Association in 1948-1958 and who were exposed to both internally deposited plutonium and external gamma radiation. Comparisons with Russian and U.S. general population rates indicate excess mortality, especially among females, plutonium plant workers, and workers with external doses exceeding 1 Sv. Comparisons within the Mayak worker cohort, which evaluate the role of plutonium body burden with adjustment for cumulative external dose, indicate excess mortality among workers with burdens estimated to exceed 7.4 kBq (relative risk = 7.9; 95% CI = 1.6-32) and among workers in the plutonium plant who did not have routine plutonium monitoring data based on urine measurements (relative risk = 4.1; 95% CI = 1.2-14). In addition, analyses treating the estimated plutonium body burden as a continuous variable indicate increasing risk with increasing burden (P < 0.001). Because of limitations in current plutonium dosimetry, no attempt was made to quantify bone cancer risks from plutonium in terms of organ dose, and risk from external dose could not be reliably evaluated.     

Mayak worker study: an improved biokinetic model for reconstructing doses from internally deposited plutonium

The plutonium production facility known as the Mayak Production Association was put into operation in June 1948. A high incidence of cancer in the Mayak workers has been related to the level of exposure to plutonium, but uncertainties in tissue doses have hampered development of dose-risk relationships. As part of an effort to improve dose estimates for these workers, the systemic biokinetic model for plutonium currently recommended by the International Commission on Radiological Protection (ICRP) has been modified to reflect recently developed data and facilitate interpretation of case-specific information. This paper describes the proposed model and discusses its implications for dose reconstruction for the Mayak workers.     

A registry for exposure and population health in the Altai region affected by fallout from the Semipalatinsk nuclear test site

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. Received: 3 March 1999 / Accepted in revised form: 8 June 1999     

Stable chromosome aberrations in the lymphocytes of a population living in the vicinity of the Semipalatinsk nuclear test site

SalomaTranslocation analysis using FISH (fluorescence in situ hybridization) chromosome painting was performed to evaluate the magnitude of exposure to ionizing radiation among the human population living close to the Semipalatinsk nuclear test site in Kazakhstan. We studied two generations of people living in villages that were in the path of the radioactive cloud from the first Soviet surface nuclear test performed in August 1949 and from later tests. The older generation (P(0)) lived in the area at the time of testing, and the younger generation (F(1)) was exposed to smaller doses from the residual fallout and later tests. In both P(0) and F(1) generations, similar translocation frequencies were observed in persons living in either the Semipalatinsk area or a noncontaminated area. Assuming translocation stability in peripheral blood lymphocytes over several decades, these findings suggest that on average, the magnitude of exposure of this cohort in the Semipalatinsk area has been considerably smaller than that reported in the literature. Previously reported doses of the order of 1-4.5 Gy (mean 2.9 Gy in the P(0) generation) cannot be confirmed by the present data.     

Risks of circulatory diseases among Mayak PA workers with radiation doses estimated using the improved Mayak Worker Dosimetry System 2008

The new Mayak Worker Dosimetry System 2008 (MWDS-2008) was published in 2013 and supersedes the Doses-2005 dosimetry system for Mayak Production Association (PA) workers. It provides revised external and internal dose estimates based on the updated occupational history data. Using MWDS-2008, a cohort of 18,856 workers first employed at one of the main Mayak PA plants during 1948–1972 and followed up to 2005 was identified. Incidence and mortality risks from ischemic heart disease (IHD) (International Classification of Diseases (ICD)-9 codes 410–414) and from cerebrovascular diseases (CVD) (ICD-9 codes 430–438) were examined in this cohort and compared with previously published risk estimates in the same cohort based on the Doses-2005 dosimetry system. Significant associations were observed between doses from external gamma-rays and IHD and CVD incidence and also between internal doses from alpha-radiation and IHD mortality and CVD incidence. The estimates of excess relative risk (ERR)/Gy were consistent with those estimates from the previous studies based on Doses-2005 system apart from the relationship between CVD incidence and internal liver dose where the ERR/Gy based on MWDS-2008 was just over three times higher than the corresponding estimate based on Doses-2005 system. Adjustment for smoking status did not show any effect on the estimates of risk from internal alpha-particle exposure.