Chronic bronchitis incidence in the extended cohort of Mayak workers first employed during 1948-1982.

OBJECTIVES: This paper describes findings from the study of chronic bronchitis (CB) incidence after occupational exposure to ionising radiation among workers employed at Russian Mayak Production Association (PA) during 1948 and 1982 and followed up until 2008 based on 'Mayak Worker Dosimetry System 2008'. METHODS: Analyses were based on 2135 verified cases among 21 417 workers. Rate ratios (RR) were estimated by categorical analysis for non-radiation and radiation factors. Excess rate ratios per Gy (ERR/Gy) of external or internal exposures with adjustments via stratification on other factors were calculated. RESULTS: The interesting finding in relation to non-radiation factors was a sharp increase in the RR for CB incidence before 1960, which could be caused by a number of factors. Analyses restricted to the follow-up after 1960 revealed statistically significant associations of the CB incidence and external γ-ray radiation, ERR/Gy=0.14 (95% CI 0.02 to 0.28) having adjusted for sex, attained age, calendar period, plant, smoking status and lung α-particle dose, and internal α-particle radiation, ERR/Gy=1.14 (95% CI 0.41 to 2.18) having adjusted for sex, attained age, calendar period, plant, smoking status and lung γ-ray dose and ERR/Gy=1.19 (95% CI 0.32 to 2.53) having additionally adjusted for pre-employment occupational hazards and smoking index instead of smoking status. CONCLUSIONS: Analyses of CB incidence in the study cohort identified positive significant association with occupational exposure to radiation: however, there are no similar studies of CB incidence in relation to radiation in other cohorts to date with which a meaningful comparison of the results could be made.

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.

[Role of occupational radiation in oncologic morbidity among "Mayak" production association workers].

Retrospective study with "case-control" method revealed increased risk of gastric cancer among "Mayak" production association workers subjected to prolonged general external gamma-radiation in overall dose over 3.0 Gy. Major role in gaster cancer among "Mayak" production association workers was played by nonradiation factors: chronic gastritis with hyposecretion, peptic ulcer, cigarette smoking, alcohol abuse.

Modeling of respiratory system dysfunction among nuclear workers: a preliminary study.

Numerous studies have reported on cancers among Mayak Production Association (PA) nuclear workers. Other studies have reported on serious deterministic effects of large radiation doses for the same population. This study relates to deterministic effects (respiratory system dysfunction) in Mayak workers after relatively small chronic radiation doses (alpha plus gamma). Because cigarette smoke is a confounding factor, we also account for smoking effects. Here we present a new empirical mathematical model that was introduced for simultaneous assessment of radiation and cigarette-smoking-related damage to the respiratory system. The model incorporates absolute thresholds for smoking- and radiation-induced respiratory system dysfunction. As the alpha radiation dose to the lung increased from 0 to 4.36 Gy, respiratory function indices studied decreased, although remaining in the normal range. The data were consistent with the view that alpha radiation doses to the lung above a relatively small threshold (0.15 to 0.39 Gy) cause some respiratory system dysfunction. Respiratory function indices were not found to be influenced by total-body gamma radiation doses in the range 0-3.8 Gy when delivered at low rates over years. However, significant decreases in airway conductance were found to be associated with cigarette smoking. Whether the indicated cigarette smoking and alpha radiation associated dysfunction is debilitating is unclear.

Influence of alpha and gamma radiations and non-radiation risk factors on the incidence of malignant liver tumors among Mayak PA workers.

This Mayak worker-based study focuses on evaluating possible associations between malignant liver cancers and chronic alpha irradiation, chronic gamma irradiation, and non-radiation risk factors (alcohol consumption, smoking, viral hepatitis, chemical exposure, and chronic digestive diseases). This is the first multivariate study related to liver cancer among Mayak workers. The study was performed using the nested, case-control approach and includes 44 cases of malignant liver tumors diagnosed from 1972 to 1999, and 111 matched controls. Adjusted odds ratio (OR(ad)) was evaluated relative to a group of workers with alpha radiation doses to liver (D(alpha)) < 2.0 Gy. Dose estimates of D(alpha) > 2.0 Gy (corresponding (239)Pu body burden estimates >20.4 kBq) were significantly associated (p < 0.003) with the occurrence of hemangiosarcomas (HAS) but only marginal significance (0.05 < p < 0.1) was found for hepatocellular cancers (HCC). The ORad for HAS was 41.7 [95% confidence interval (CI): 4.6, 333] for a group with D(alpha) in the range >2.0-5.0 Gy and was 62.5 (7.4, 500) for a group with D(alpha) > 5.0-16.9 Gy. The attributable risk (AR) was calculated as 82%. For HCC, O(Rad) was estimated as 8.4 (0.8, 85.3; p < 0.07) for a group with D(alpha) in the range >2.0-9.3 Gy. For the indicated group, the AR was 14%. An association with high external gamma-ray doses (D(gamma)) to the total body was revealed for both HCC and for combined liver cancers when dose was treated as a continuous variable. However, we find no evidence that chronic low doses of gamma rays are associated with liver cancer occurrence. Cholangiocarcinoma (CHC) was not associated with either alpha- or gamma-ray exposure. As expected, an association between alcohol abuse and HCC was inferred [O(Rad) = 3.3 (1.2, 9); AR = 41%] but not for CHC or HAS.

Chromosomal aberrations in lymphocytes of peripheral blood among Mayak facility workers who inhaled insoluble forms of 239PU.

A cytogenetic study was performed on 79 plutonium (Pu) workers chronically exposed to alpha radiation from inhaled, low-transportable (insoluble) compounds of airborne 239Pu and to external gamma rays. Body burden estimates for 239Pu ranged from 0 to 15.5 kBq. Chromosomal aberrations (CAs) (stable and unstable) among peripheral blood lymphocytes and cumulative alpha radiation doses were evaluated approximately 25 y after first contact with 239Pu. For the cytogenetic analyses, a standard two-day peripheral blood lymphocyte culture technique was applied. While alpha radiation doses continually increase up to the time of cytogenetic measurements, significant gamma ray exposures essentially ceased long before the time of measurement, so that alpha and gamma doses were not correlated. For the exposed workers, the mean 239Pu body burden (estimate), evaluated at the time of the cytogenetic measurement, was 1.23 +/- 0.26 kBq and the corresponding mean absorbed external gamma ray dose (estimate) to the total body was 0.076 +/- 0.009 Gy. Single and multivariate regression analyses were performed on the CA data. Stable, unstable and total aberrations increased as the 239Pu body burden increased over the range 0-4.5 kBq. However, above this range little additional increase was observed. CAs were weakly correlated with time since the first intake of 239Pu. No relationship between chromatid aberrations and 239Pu incorporation was found. Unstable (but not stable) aberrations were correlated with gamma radiation dose. No significant relationship of CA and smoking was found.

Interaction of radiation and smoking in lung cancer induction among workers at the Mayak nuclear enterprise.

For radiation-related cancer risk evaluation, it is important to assess not only influences of individual risk factors but also their interactive effects (e.g., additive, multiplicative, etc.). Multivariate analysis methods adapted for interactive effects allow such assessments. We have used a multivariate analysis approach to investigate the pair-wise interactions of the previously identified three main etiological factors for lung cancer induction in Russian workers of the Mayak Production Association (PA) nuclear enterprise. These three factors are as follows: (1) body burden of inhaled plutonium-239 (239Pu), an influence on absorbed alpha-radiation dose; (2) cumulative, absorbed external gamma-radiation dose to the lung; and (3) level of cigarette smoking as indicated by a smoking index (SI). The SI represents the cigarettes smoked per day times years smoking. The Mayak PA workers were exposed by inhalation to both soluble and insoluble forms of 239Pu. Based on a cohort of 4,390 persons (77% male), we conducted a nested, case-control study of lung cancer induction using 486 matched cases and controls. Each case was matched to two controls. Matching was based on five factors: sex, year of birth, year work began, profession, and workplace. Three levels of smoking were considered: low (SI = 1 to 499), used as a reference level; middle (SI = 500 to 900); and high (SI = 901 to 2,000). For lung cancer induction, a supra-multiplicative effect was demonstrated for high external gamma-ray doses (> 2.0 Gy) plus high 239Pu intakes (body burden >2.3 kBq). This observation is consistent with the hypothesis of curvilinear dose-response relationships for lung cancer induction by high- and low-LET radiations. The interaction between radiation (external gamma rays or 239Pu body burden) and cigarette smoke was found to depend on the smoking level. For the middle level of smoking in combination with gamma radiation (> 2.0 Gy) or 239Pu body burden (> 2.3 kBq), results were consistent with additive effects. However, for the high level of smoking in combination with gamma radiation (> 2.0 Gy) or 239Pu body burden (> 2.3 kBq), results were consistent with the occurrence of multiplicative effects. These results indicate that low-dose risk estimates for radiation-induced lung cancer derived without adjusting for the influence of cigarette smoking could be greatly overestimated. Further, such systematic error may considerably distort the shape of the risk vs. dose curve and could possibly obscure the presence of a dose threshold for radiation-induced lung cancer.

[Genotype analysis of biochemical status in people irradiated with significant doses of radiation]. / Genotipicheskii analiz biokhimicheskogo statusa u liudei, obluchennykh v znachitel'nykh dozakh.

416 workers of the enterprise of a nuclear industry aged from 52 to 78 years exposed to chronic influence of external gamma-irradiation in summary dozes 1.0-7.56 Gy and plutonium-239 incorporation, (in 32.3% of cases exceeding the allowable limit) were studied. A correlation between a complex of 26 biochemical and immunochemical parameters and the radiating factors was investigated at different haptoglobin genotypes (Hp). It was established, that the greatest number of changes of biochemical parameters related to radiating influence, was observed at the people with a genotype Hp 2-2 (7 parameters), to a lesser degree--at a genotype Hp 2-1 (5 parameters) and in some more smaller degree--at a genotype Hp 1-1 (4 parameters). All investigated people with a genotype 2-2 were characterised by increase of serum protein entropy.

[Interactions of radiation factors and smoking in the etiology of lung cancer in workers of atomic enterprises]. / Vzaimodeistvie radiatsionnykh faktorov i kureniia pri razvitii raka legkogo u rabotnikov atomnogo predpriiatiia.

It was shown on the basis of retrospective investigation of 500 workers at a nuclear enterprise (162 cases of lung cancer, 338 persons as matching control) that the interaction of external gamma-irradiation (> 2.0 Gy) and the body-burden of 239Pu (> 9.3 kBq) at lung cancer incidence in multiplicative. Combined influence of smoking and radiation factors was found dependent on smoking index (SI): it changed from additive up to multiplicative and than to antagonistic with the increase of the smoking effect. The received results could be explained on the basis of a two-mutation model of radiation carcinogenesis.

[Uric acid in blood serum and incidence of hyperuricemia in irradiated people. Connection with radioactive and nonradioactive factors]. / Mochevaia kislota syvorotki krovi i rasprostranennost' giperurikemii u obluchennykh liudei, sviaz' s radiatsionnymi i neradiatsionnymi faktorami.

A total of 1,002 workers aged 36 to 72 years who were engaged in atomic industry and exposed to external gamma-irradiation and incorporated plutonium 239 in a wide dosage range. The levels of uric acid (UA), the incidence of hyperuricemia and their association with 2 radiation and 12 nonradiation factors were studied in the examinees. There was a positive correlation between the purine metabolic parameters and the total dosage of external gamma-irradiation, sex (UC levels were higher in males than in females), body weight index, essential hypertension, and the type of haptoglobin 1-1. The influence of nonradiation factors on the parameters in question were substantially greater than that of external irradiation. Linear regression equations were derived for the dependence of the levels of UA and hyperuricemia upon the influencing factors.

[Distribution of haptoglobin types and their significance in biochemical and immunologic indicators in persons exposed to low radiation doses]. / Raspredelenie tipov gaptoglobina i ikh znachenie v izmeneniiakh biokhimicheskikh i immunologicheskikh pokazatelei u liudei, obluchennykh v malykh dozakh.

Haptoglobin (Hp) polymorphism and its significance for changes in biochemical and immunological parameters was analyzed in personnel of a nuclear plant receiving doses of external and internal irradiation close to maximum permissible levels. The distribution of Hp types and frequencies of alleles Hp in the group of probands asa a whole (1-1 - 14.1%; 2-1 - 49.2%; and 2-2 - 36.7%) and in probands subjected to different types and doses of irradiation (1-1, 13.6 - 16.0%; 2-1, 47.8 - 50.5%; and 2-2:35.8 - 38.2%) did not differ from those expected or from corresponding parameters of the control group and population. An increase in the frequency of allele Hp was observed for persons over 60 years of age. It was found that the levels of uric acid, the activities of acid phosphatase, lactate dehydrogenase, alkaline phosphatase and its isozymes, and the content of certain lymphocyte classes and immune complexes are initially higher in carriers of Hp type 1-1. In these probands, changes in certain parameters related to irradiation were observed less frequently. In some cases, opposite changes in immunological parameters were observed in persons with different Hp types after internal irradiation.