Cerebrovascular diseases incidence and mortality in an extended Mayak Worker Cohort 1948-1982.

Incidence and mortality from cerebrovascular disease (CVD) [International Classification of Diseases 9th revision (ICD-9) codes: 430-438] was studied in a cohort of 22,377 workers first employed at the Mayak Production Association (Mayak PA) in 1948-1982 and followed up to the end of 2008. The cohort size was increased by 19% and follow-up extended by 3 years over the previous analysis. Radiation doses were estimated using an updated dosimetry system: Mayak Worker Dosimetry System 2008 (MWDS-2008). For the first time, in an analysis of this cohort, quantitative smoking data were used. Workers of the study cohort were exposed occupationally to prolonged external gamma rays and internal alpha particles. The mean (±standard deviation) total dose from external gamma rays was 0.54 ± 0.76 Gy (95% percentile 2.21 Gy) for males and 0.44 ± 0.65 Gy (95% percentile 1.87 Gy) for females. The mean plutonium body burden in the 31% of workers monitored for internal exposure was 1.32 ± 4.87 kBq (95% percentile 4.71 kBq) for males and 2.21 ± 13.24 kBq (95% percentile 4.56 kBq) for females. The mean total absorbed alpha-particles dose to the liver from incorporated plutonium was 0.23 ± 0.77 Gy (95% percentile 0.89 Gy) in males and 0.44 ± 2.11 Gy (95% percentile 1.25 Gy) in females. After adjusting for nonradiation factors (gender, age, calendar period, employment period, facility, smoking, alcohol consumption), there were significantly increasing trends in CVD incidence associated with total absorbed dose from external gamma rays and total absorbed dose to the liver from internal alpha-particle radiation exposure. Excess relative risks per Gy (ERR/Gy) were 0.46 (95% CI 0.37, 0.57) and 0.28 (95% CI 0.16, 0.42), respectively, based on a linear dose-response model. Adjustments for additional factors (hypertension, body mass index, duration of employment, smoking index and total absorbed dose to the liver from internal exposure during the analysis of external exposure and vice versa) had little effect on the results. The categorical analyses showed that CVD incidence was significantly higher among workers with total absorbed external gamma-ray doses greater than 0.1 Gy compared to those exposed to lower doses and that CVD incidence was also significantly higher among workers with total absorbed internal alpha-particle doses to the liver from incorporated plutonium greater than 0.01 Gy compared to those exposed to lower doses. The results of the categorical analyses of CVD incidence were in good agreement with a linear dose response for external gamma-ray doses but for internal alpha-particle doses the picture was less clear. For the first time an excess risk of CVD mortality was seen in workers whose livers were exposed to internal alpha-particle doses greater than 0.1 Gy compared to those workers who were exposed to doses of less than 0.01 Gy. A significant increasing trend for CVD mortality with internal alpha-particle dose was revealed in the subcohort of workers exposed at doses <1.0 Gy after having adjusted for nonradiation factors, ERR/Gy = 0.84 (95% CI, 0.09, 1.92). These updated results provide good evidence for a linear trend in risk of CVD incidence with external gamma-ray dose. The trend for CVD incidence with internal alpha-particle dose is less clear due to the impact of issues concerning the use of dose estimates based on below the limit of detection bioassay measurements.

Chronic bronchitis in the cohort of Mayak workers first employed 1948-1958.

Incidence of chronic bronchitis has been studied in a cohort of 12,210 workers first employed at one of the main plants of the Mayak nuclear facility during 1948-1958 and followed up to 31 December 2005. Information on external gamma doses is available for virtually all of these workers; in contrast, plutonium body burden was measured only for 30% of workers. During the follow-up period in the study cohort 1,175 incident cases of chronic bronchitis were verified. The analyses of nonradiation factors revealed that the underlying risk of chronic bronchitis incidence increased with increasing attained age and was higher among smokers compared with never-smokers as would be expected. The most interesting finding in relationship to nonradiation factors was a sharp increase in the baseline chronic bronchitis risk before 1960. The cause of this is not clear but a number of factors may play a role. Based on the follow-up data after 1960, the analysis showed a statistically significant linear dose response relationship with cumulative external gamma-ray dose (ERR/Gy = 0.14, 95% CI 0.01, 0.32). Based on the same subset but with an additional restriction to members with cumulative internal lung dose below 1 Gy, a statistically significant linear dose response relationship with internal alpha-radiation lung dose from incorporated plutonium was found (ERR/Gy = 2.70, 95% CI 1.20, 4.87). In both cases, adjustment was made for nonradiation factors, including smoking and either internal or external dose as appropriate. At present there are no similar incidence studies with which to compare results. However, the most recent data from the atomic bomb survivor cohort (the Life Span Study) showed statistically significant excess mortality risk for respiratory diseases of 22% per Gy and this value is within the confidence bounds of the point estimate of the risk from this study in relation to external dose.

[Risk of cerebrovascular disease incidence in the cohort of Mayak production association workers first employed during 1948-1958].

Incidence of cerebrovascular diseases (CVD) has been studied in a cohort of 12210 workers first employed at one of the main plants (reactors, radiochemical or plutonium) of the Mayak nuclear facility during 1948-1958 and followed up to the end of 2000. Information on external gamma doses is available for virtually all (99.9%) of these workers; the mean (+/- one standard deviation) total gamma dose was 0.91 +/- 0.95 Gy (99% percentile 3.9 Gy) for men and 0.65 +/- 0.75 Gy (99% percentile 2.99 Gy) for women. Plutonium body burden was measured only for 30.0% of workers. Amongst those monitored, the mean (+/- standard deviation) cumulative liver dose from plutonium alpha exposure was 0.40 +/- 1.15 Gy (99% percentile 5.88 Gy) for men and 0.81 +/- 4.60 Gy (99% percentile 15.95 Gy) for women 4418 cases (first diagnosis) of CVD were identified in the studied cohort. A statistically significant increasing trend in CVD incidence with total external gamma dose was revealed after adjustment for non-radiation factors and internal exposure from incorporated plutonium-239. Excess relative risk per Gy was 0.464 (95% confidence interval 0.360-0.567). Incidence of CVD was statistically significantly higher for the workers chronically exposed to external gamma rays at a dose above 1.0 Gy A statistically significant increasing trend in CVD incidence with internal liver dose from plutonium alpha exposure was observed after adjustment for non-radiation factors and external exposure. ERR per Gy was 0.155 (95% confidence interval 0.075-0.235). CVD incidence was statistically significantly higher among workers with a plutonium liver dose above 0.1 Gy, although the trend estimates differed between workers at different plants. The incidence risk estimates for external radiation are generally compatible with estimates from the study of Chernobyl clean-up workers, although the incidence data point to higher risk estimates compared to those from the Japanese A-bomb survivors.

[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 the cohort of workers first employed at Mayak PA in 1948-1958.

The incidence of and mortality from cerebrovascular diseases (CVD) have been studied in a cohort of 12,210 workers first employed at one of the main plants of the Mayak nuclear facility during 1948-1958 and followed up to 31 December 2000. Information on external γ-ray doses is available for virtually all of these workers (99.9%); the mean total γ-ray dose (± SD) was 0.91 ± 0.95 Gy (99th percentile 3.9 Gy) for men and 0.65 ± 0.75 Gy (99th percentile 2.99 Gy) for women. In contrast, plutonium body burden was measured only for 30.0% of workers; among those monitored, the mean cumulative liver dose from plutonium α-particle exposure (± SD) was 0.40 ± 1.15 Gy (99th percentile 5.88 Gy) for men and 0.81 ± 4.60 Gy (99th percentile 15.95 Gy) for women. A total of 4418 cases of CVD, including 665 cases of stroke, and 753 deaths from CVD, including 404 deaths from stroke, were identified in the study cohort. Having adjusted for non-radiation factors, there were statistically significant increasing trends in CVD incidence but not mortality with both total external γ-ray dose and internal liver dose. Much of the evidence for increased incidence in relation to external dose arose for workers with cumulative doses above 1 Gy. Although the dose response is consistent with linearity, the statistical power to detect non-linearity at external doses below 1 Gy was low. CVD incidence was statistically significantly higher among workers with a plutonium liver dose above 0.1 Gy. There was a statistically significant increasing trend in incidence with increasing internal dose, even after adjusting for external dose, although the trend estimates differed between workers at different plants. The risk estimates for external radiation 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.

Cardiovascular diseases in the cohort of workers first employed at Mayak PA in 1948-1958.

Incidence of and mortality from cardiovascular diseases have been studied in a cohort of 12,210 workers first employed at one of the main plants of the Mayak nuclear facility during 1948-1958 and followed up to 31 December 2000. Information on external gamma-ray doses is available for virtually all of these workers (99.9%); the mean total gamma-ray dose (+/-SD) was 0.91 +/- 0.95 Gy (99% percentile 3.9 Gy) for men and 0.65 +/- 0.75 Gy (99% percentile 2.99 Gy) for women. In contrast, plutonium body burden was measured for only 30.0% of workers; among those monitored, the mean cumulative liver dose from plutonium alpha exposure (+/- SD) was 0.40 +/- 1.15 Gy (99% percentile 5.88 Gy) for men and 0.81 +/- 4.60 Gy (99% percentile 15.95 Gy) for women. A total of 3751 cases of ischemic heart disease (IHD), including 683 cases of acute myocardial infarction (AMI), and 1495 IHD deaths, including 338 AMI deaths, were identified in the study cohort during the follow-up period. Having adjusted for non-radiation factors, there were statistically significant increasing trends with both total external gamma-ray dose and internal liver dose in IHD incidence. The trend with internal dose was weaker and was not statistically significant after adjusting for external dose, whereas the external dose trend was little changed after adjusting for internal dose. The trend with external dose in IHD mortality was not statistically significantly greater than zero but was consistent with the corresponding trend in IHD incidence. The estimated trend in IHD mortality with internal dose was lower and was not statistically significant once adjustment was made for external dose. There was a statistically significantly increasing trend in AMI incidence but not AMI incidence with external dose. The risk estimates for IHD in relation to external radiation are generally compatible with those from other large occupational studies and the Japanese A-bomb survivors.

Mortality and cancer incidence following occupational radiation exposure: third analysis of the National Registry for Radiation Workers.

Mortality and cancer incidence were studied in the National Registry for Radiation Workers in, relative to earlier analyses, an enlarged cohort of 174 541 persons, with longer follow-up (to 2001) and, for the first time, cancer registration data. SMRs for all causes and all malignant neoplasms were 81 and 84 respectively, demonstrating a 'healthy worker effect'. Within the cohort, mortality and incidence from both leukaemia excluding CLL and the grouping of all malignant neoplasms excluding leukaemia increased to a statistically significant extent with increasing radiation dose. Estimates of the trend in risk with dose were similar to those for the Japanese A-bomb survivors, with 90% confidence intervals that excluded both risks more than 2-3 times greater than the A-bomb values and no raised risk. Some evidence of an increasing trend with dose in mortality from all circulatory diseases may, at least partly, be due to confounding by smoking. This analysis provides the most precise estimates to date of mortality and cancer risks following occupational radiation exposure and strengthens the evidence for raised risks from these exposures. The cancer risk estimates are consistent with values used to set radiation protection standards.

Epidemiological studies of UK test veterans: II. Mortality and cancer incidence.

An epidemiological study was set up in the 1980s of UK participants in the UK atmospheric nuclear weapons testing programme. A large cohort of test participants was established along with a closely matched comparison or control group. Three analyses of mortality and cancer incidence have been carried out. This review describes the development of the evidence on possible effects on test participants with especial emphasis on the most recent analysis. Other sources of evidence, particularly from studies of other groups of test participants, are also considered. It was concluded that overall levels of mortality and cancer incidence in UK nuclear weapons test participants were similar to those in a matched control group, and overall mortality was lower than expected from national rates. There was no evidence of an increased raised risk of multiple myeloma among test participants in recent years, and the suggestion in the first analysis of this cohort of a raised myeloma risk relative to controls is likely to have been a chance finding. There was some evidence of a raised risk of leukaemia other than chronic lymphatic leukaemia among test participants relative to controls, particularly in the early years after the tests. Whilst this could be a chance finding, the possibility that test participation caused a small absolute risk of leukaemia other than chronic lymphatic leukaemia cannot be ruled out.

Cancer in the offspring of radiation workers: an investigation of employment timing and a reanalysis using updated dose information.

An earlier case-control study found no evidence of paternal preconceptional irradiation (PPI) as a cause of childhood leukaemia and non-Hodgkin's lymphoma (LNHL). Although fathers of children with LNHL were more likely to have been radiation workers, the risk was most marked in those with doses below the level of detection. The timing of paternal employment as a radiation worker has now been examined. The previously reported elevated risk of LNHL in the children of male radiation workers was limited to those whose fathers were still radiation workers at conception or whose employment also continued until diagnosis. Children whose fathers stopped radiation work prior to their conception were found to have no excess risk of LNHL. It was not possible to distinguish between the risks associated with paternal radiation work at conception and at the time of diagnosis. A reanalysis of the original study hypothesis incorporating updated dosimetric information gave similar results to those obtained previously. In particular, the risks of LNHL did not show an association with radiation doses received by the father before conception. It seems likely that the increased risk of LNHL among the children of male radiation workers is associated with an increased exposure to some infective agent consequent on high levels of population mixing.

Follow up of mortality and incidence of cancer 1952-98 in men from the UK who participated in the UK's atmospheric nuclear weapon tests and experimental programmes.

AIMS: To extend and analyse follow up of mortality and cancer incidence among men who took part in the UK's atmospheric nuclear weapon tests and experimental programmes 40-50 years ago, with particular reference to multiple myeloma and leukaemia. METHODS: A total of 21,357 servicemen and male civilians from the UK who participated in the tests and a control group of 22,333 male controls were followed over the period 1952-98. Analyses were conducted of mortality from various causes, and of mortality and incidence for 27 types of cancer. RESULTS: Rates of mortality from all causes continued to be similar among test participants and controls with the longer follow up, with standardised mortality ratios (SMRs) of 89 and 88 respectively over the full follow up period. For all cancers, the corresponding SMRs were 93 for participants and 92 for controls. Mortality from multiple myeloma was consistent with national rates both for participants and controls, and the relative risk (RR) of myeloma incidence among participants relative to controls was 1.14 (90% CI 0.74 to 1.74) over the full follow up period and 0.79 (90% CI 0.45 to 1.38) during the extended period of follow up (1991-98). Over the full follow up period, leukaemia mortality among participants was consistent with national rates, while rates among controls were significantly lower, and there was a suggestion of a raised risk among test participants relative to controls (RR 1.45, 90% CI 0.96 to 2.17); the corresponding RR for leukaemia incidence was 1.33 (90% CI 0.97 to 1.84). After excluding chronic lymphatic leukaemia (CLL), which is not thought to be radiation inducible, the RR of leukaemia mortality increased to 1.83 (90% CI 1.15 to 2.93), while that for incidence was little changed. Analysis of subgroups of participants with greater potential for exposure provided little evidence of increased risks, although the numbers of men involved were smaller and the statistical power was therefore less. Among other types of cancer, only for liver cancer incidence was there evidence of differences in rates between participants and controls in both the earlier and in the additional period of follow up. Mortality rates among test participants from causes other than cancer were generally similar to those among the controls. CONCLUSIONS: Overall levels of mortality and cancer incidence in UK nuclear weapons test participants have continued to be similar to those in a matched control group, and overall mortality has remained lower than expected from national rates. There was no evidence of an increased raised risk of multiple myeloma among test participants in recent years, and the suggestion in the first analysis of this study of a raised myeloma risk is likely to have been a chance finding. There was some evidence of a raised risk of leukaemia other than CLL among test participants relative to controls, particularly in the early years after the tests, although a small risk may have persisted more recently. This could be a chance finding, in view of low rates among the controls and the generally small radiation doses recorded for test participants. However, the possibility that test participation caused a small absolute risk of leukaemia other than CLL cannot be ruled out.

Modelling lung tumour risk in radon-exposed uranium miners using generalizations of the two-mutation model of Moolgavkar, Venzon and Knudson.

PURPOSES: To model radon-induced lung cancer in uranium miners using a quasi-biological model of carcinogenesis. MATERIALS AND METHODS: Fitting of generalizations of the stochastic two-mutation carcinogenesis model of Moolgavkar, Venzon and Knudson to a case-control dataset nested within the cohort and to the full cohort of lung cancer mortality in the Colorado Plateau uranium miners, taking account of exposure to cigarette smoke and to radon daughters. RESULTS: Models with three mutations gave adequate descriptions of the time and age patterns of radon-daughter-induced excess lung tumour mortality. The overall fit of the two-mutation model to the case-control data was somewhat worse than that of the three-mutation model. For both the optimal two- and three-mutation models radon daughters and cigarette smoke were assumed to act on the first mutation rate. In the optimal two-mutation model, radon daughters also modified the intermediate cell death or differentiation rate. In the optimal three-mutation model, radon daughters modified the second mutation rate. In all models, the action of radon daughters and cigarette smoke was markedly non-linear, particularly in their action on the mutation rates. The optimal two- and three-mutation models fitted to the cohort data were of slightly different form to those fitted to the case-control data. The model fits to the cohort data are preferred to those to the case-control data on grounds of plausibility. CONCLUSIONS: Quasi-biological carcinogenesis models with three mutations give adequate descriptions of the time and age patterns of radon-daughter-induced excess lung tumour mortality. The overall fit of the two-mutation model is somewhat worse than that of the three-mutation model.