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.

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.

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.

[Health status among the staff at the nuclear waste processing plant]. / Sostoianie zdorov'ia personala zavoda po pererabotke otrabotavshego iadernogo topliva.

Based on annual medical examinations over 20 years, the authors evaluated health state of stuffers (423 individuals) who work at the first Russian plant treating nuclear fuel waste. Over the stated time no hematologic, neurologic and other syndromes and diseases caused by radiation were revealed. Moderate increase in platelet and WBC counts appeared in first years of work (adaptive response) and higher parameters of bronchial obstruction in smokers. The article presents incidence and structure of the diseases first revealed.

Deterministic effects from occupational radiation exposures in a cohort of Mayak PA workers: data base description.

Project 2.3 of the Joint Coordinating Committee on Radiation Effects Research (JCCRER) is a study of deterministic health effects among a cohort of Russia nuclear workers. The preliminary study population includes a stratified random sample of 221 radiation workers who were employed in a cohort of 8,055 workers at the Mayak PA facilities for at least one year during the period from 1948 to 1958. High annual doses, approaching 1 Gy per year from external and internal radiation sources, were reported for a significant proportion of the workers in this cohort. The present data set includes 96 cases of chronic radiation sickness (CRS), 14 cases of acute radiation syndrome (ARS) and 13 cases of plutonium pneumosclerosis (PPn). The remainder of the sample consists of "uninjured workers" who had no known history of radiation illness or injury; however, the uninjured workers are not "controls" for radiation exposure. The data base is currently being expanded to 600 individuals sampled from the cohort of workers from 1948 to 1958 to allow a more complete analysis of the deterministic health effects and comparisons with existing health effect models. The final data base will be used with state-of-the-art modeling techniques to determine threshold doses and dose-response relationships for key clinical diagnostic variables.

Multifactorial analysis of lung cancer dose-response relationships for workers at the Mayak nuclear enterprise.

Dose-response relationships for alpha-radiation-induced lung cancers (adenocarcinoma, squamous carcinoma and small cell carcinoma) were developed by multifactorial analysis using data for Mayak nuclear enterprise workers chronically exposed by inhalation to 239Pu. The three most important lung cancer risk factors (smoking, plutonium incorporation, and external gamma irradiation), out of six factors previously identified, were used. Relative risks (odds ratios) were determined for 500 nuclear enterprise workers (162 cancer cases, 338 control) for different dose levels using a case-control study design and logistic regression. A threshold at about 3.7 kBq or 0.80 Gy was discovered for incorporated plutonium, which is satisfactorily described by linear-quadratic and quadratic models. Excess relative risk was 0.020 kBq(-2) and 0.97 Gy(-2). This quadratic function was mainly due to adenocarcinoma. A trend for decreasing risk was noted for the lowest levels of plutonium incorporation, near permissible level. No clear-cut dose-response relationship for lung cancer induction by chronic external gamma irradiation was obtained. Lung cancer induction by cigarette smoking had a linear dependence: smoking of one pack of papiroses (a type of Russian cigarette) per day for 5 y increases the lung cancer risk twofold. The effect was most clearly manifested for squamous-cell carcinoma.

The influence of radiation and nonradiation factors on the lung cancer incidence among the workers of the nuclear enterprise Mayak.

For the estimation of radiation lung cancer risk for a human being it is important to take into account different etiological factors because of the polyetiology of this disease. This work was the aim of a retrospective investigation ("case-control") of 500 workers of a nuclear enterprise that had been gamma-irradiated in a wide dose range and had had exposure to airborne 239Pu. One hundred sixty-two persons contracted lung cancer (morbidity), and 338 persons that had not fallen ill served as pair control. Eleven potential risk factors were evaluated using a logistic regression model, five insignificant factors were excluded, and the remaining factors were arranged (by odds ratio) in decreasing order: smoking > plutonium pneumosclerosis > plutonium incorporation in body > chronic obstructive pulmonary diseases (COPD) > decrease of body mass > external gamma-irradiation. The percentage of histologically confirmed adenocarcinoma among the nuclear enterprise workers was 74%, which is significantly higher than 33% among the population that did not work at the enterprise, particularly in the case of high (more than 11 kBq) plutonium incorporation by the nuclear workers. The localization of tumors in this cohort is more frequently in the lower and middle lung lobes and at the periphery. Each of the histological types of lung cancer has manifested a different degree of correlation with particular factors. The adenocarcinoma has the most frequent correlation with the radiation factors; the odds ratio for plutonium incorporation and plutonium pneumosclerosis is 2.9 (95% CI = 1.0-8.4); for external gamma-irradiation the odds ratio is 1.9 (0.99-3.5); the odds ratio for smoking is 4.3 (1.9-9.9). The squamous-cell carcinoma has the highest correlation with non-occupational factors: with smoking the OR is 6.8 (1.2-38.7), with the chronic obstructive pulmonary diseases the odds ratio is 3.9 (1.8-8.4), and with body mass decrease the odds ratio is 2.1 (0.94-4.6); odds ratio for plutonium incorporation is 4.2 (1.4-12.8). The small-cell carcinoma has correlation with body mass decrease [odds ratio = 2.9 (1.2-7.6)] and high level of smoking [smoking index > 500; odds ratio = 3.5 (1.4-8.9)]. The portion of the occupational cancers among the workers of the nuclear enterprise, evaluated on the base of attributive risk, is 26%, with 57% for adenocarcinoma, 9% for squamous-cell carcinoma, and 8% for small-cell carcinoma. The investigation is continued to assess the dose-effect and factors interactions.