An Assessment of Radiation-Associated Risks of Mortality from Circulatory Disease in the Cohorts of Mayak and Sellafield Nuclear Workers.

Mortality from circulatory disease (CD), ischemic heart disease (IHD) and cerebrovascular disease (CeVD) was investigated in relationship to cumulative doses of external gamma radiation and internal alpha radiation to the liver from deposited plutonium over long follow-up periods in two large cohorts of nuclear workers: the Russian Mayak Worker Cohort (MWC) and the UK Sellafield Worker Cohort (SWC). The MWC comprised 22,374 workers (74.6% males) with 5,123 CD deaths registered during 842,538 person-years of follow-up, while the SWC comprised 23,443 workers (87.8% males) with 2,322 CD deaths registered during 602,311 person-years of follow-up. Dose estimates for external gamma radiation and internal alpha radiation to the liver were calculated via a common methodology, in accordance with an agreed protocol. The mean cumulative external Hp(10) dose was 0.52 Sv for the MWC and 0.07 Sv for the SWC, while the mean cumulative internal dose was 0.19 Gy for the MWC and 0.01 Gy for the SWC. Categorical relative risks (RR) and excess relative risks (ERR) per unit dose were estimated for each cohort and for the pooled cohort when appropriate. The dose responses for CD, IHD and CeVD in relationship to internal alpha-particle dose did not differ significantly from the null for either the MWC, the SWC or the pooled plutonium worker cohort. The ERR/Sv estimates in relationship to external exposure were significantly raised for both cohorts (marginally so for the MWC) for CD and IHD (but not for CeVD), but differed significantly between the two cohorts, the estimate for the SWC being approximately ten times greater than that for the MWC. Examination of the ERR/Sv estimates for two periods of first employment at the two facilities revealed that the significant heterogeneity was confined to the earlier sub-cohorts, and that the estimates for the later sub-cohorts were compatible. The two sub-cohorts for the later first-employment periods were pooled, producing risk estimates that were raised, but not significantly so: ERR/Sv for CD, IHD and CeVD of 0.22 (95% CI: -0.01, 0.49), 0.22 (95% CI: -0.06, 0.57) and 0.24 (95% CI: -0.17, 0.80), respectively. The reasons for the complex pattern of results found in this study are unclear. Among potential explanations are the influence of differences in background CD mortality rates, an effect of other occupational factors, substantial uncertainties in doses, particularly during earlier periods of operations, as well as confounding and/or modifying factors that were not taken into account in the current analysis.

[Risk of senile cataract among nuclear industry workers]. / Risk zabolevaemosti starcheskoĭ kataraktoĭ u rabotnikov predpriiatiia atomnoĭ promyshlennosti.

AIM: to assess the relative risk (RR) of senile cataract in a cohort of workers occupationally exposed to external gamma-rays over a long time period. MATERIAL AND METHODS: The RR of cataract development was studied in a cohort of nuclear workers that were first employed in 1948-1982 and followed up till the end of 2008 (n=22,377; females, 25.4%). The mean age at initial employment was 24.9 years. The mean cumulative gamma-ray dose was 0.54 Sv in males and 0.44 Sv in females. The analysis performed with EPICURE software provided RR estimates for cataract incidence in relation to a number of non-radiation and radiation factors. RESULTS: The RR of senile cataract increased with the attained age of the workers. The RR was significantly higher in males during the 2006-2008 period as compared to the 1996-2005 period. The RR was significantly higher in workers that were diagnosed with glaucoma and high myopia as compared to those that were not. The risk of senile cataract increased with the external gamma-ray dose and was the highest in workers who had formerly been exposed to doses above 2.00 Sv. The RR of senile cataract showed no dependency on sex, age at initial employment, smoking status, alcohol consumption, or diabetes mellitus. CONCLUSION: The incidence of senile cataract in the cohort under study was found to depend on both non-radiation and radiation factors.

[Risk of death from circulatory diseases in a cohort of patients exposed to chronic radiation]. / Risk smerti ot boleznei sistemy krovoobrashcheniia v kogorte rabotnikov, podvergshikhsia khronicheskomu oblucheniiu.

AIM: To assess mortality from circulatory diseases (CD) in a cohort of workers exposed occupationally to chronic radiation in relation to external and internal exposure, by taking into account known non-radiation risk factors (RFs), such as smoking (including smoking index), alcohol consumption, hypertension, and body mass index. SUBJECTS AND METHODS: Mortality from CD (ICD-10: I00 - I99) was studied in a cohort of 22,377 nuclear power plant («Mayak¼ Production Association) workers exposed occupationally to chronic radiation. The study was based on the individual dose estimates of external and internal exposure taken from the new Mayak workers dosimetry system 2008 (MWDS-2008). The quantitative characteristics of smoking (smoking index) were used for the first time to assess the risk for CD in the cohort of workers exposed to chronic radiation. RESULTS: There was a statistically significant linear relationship between CD mortality and external gamma-dose after adjusting for the non-radiation RFs; the excess relative risk per unit dose (ERR/Gy) was 0.05 (95% confidence interval (CI): 0 to 0.11). Introducing an additional adjustment for internal alpha-dose resulted in a twofold increase in ERR/Gy=0.10 (95% CI: 0.02 to 0.21). There was a statistically significant increasing trend in CD mortality with the elevated absorbed dose from internal alpha-radiation in the liver (ERR/Gy=0.27; 95% CI: 0.12 to 0.48). However, ERR/Gy decreased and lost its statistical significance after adjusting for external gamma-dose. CONCLUSION: The results of this study are in good agreement with risk estimates obtained in the Japanese cohort of atomic bomb survivors and in the cohorts of occupationally exposed workers.

[Biological Dosimetry Technique for Estimation of Doses from Accidental Exposure to External γ-Rays].

Individual doses from external γ-rays were estimated using biological dosimetry based on limited samplings (n1= 15 and n2 12 individuals) which comprised the Mayak workers group with acute radiation sickness (ARS). The following primary data were used for calculation as initial parameters: estimated dose from ex- ternal γ-rays based on physical dosimetry methods - D (Gy); time before first vomiting - T (h); number of lymphocytes in peripheral blood on a second day after acute radiation exposure - L (109/1); number of neutrophils in blood during first hours after accidental radiation exposure - N(109/). A number of mathe- matical models used for dose estimation were verified: power-law dependence of the absorbed dose from ex- ternal γ-rays (D) on time before first vomiting (7), exponential dependence of D on the number of lympho- cytes in peripheral blood (L), dependence of D on the number of neutrophils in peripheral blood (N) and complex models forD association with Tand L parameters as well as-with Tand Nparameters. The biological dosimetry technique based on a complex approach was shown to provide the best agreement with physical dosimetry methods for individual assessment of doses from external γ-rays.

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.

[Using mFISH and mBAND for Bioindication of Internal α-Radiation].

This study was aimed to compare mFISH and mBAND techniques in assessment of the yield of chromosomal aberrations induced by high-LET ionizing radiation. The study group included Mayak workers (46 individuals), for whom the yield of chromosomal aberrations was assessed using two methods: mFISH and mBAND. It was shown that both methods are applicable for biological indication of internal α-radiation exposure. Nevertheless, in case when the source of ionizing radiation is unknown or in terms of a mixed exposure, mFISH appeared as more informative technique that allows identification of markers both external γ-rays (translocations) and internal α-radiation (complex chromosomal rearrangements).

[The Influence of the Ionizing Radiation on the Development of Atherosclerosis].

The results of the epidemiological research of the last decade demonstrate the increased risk of circulatory system diseases in the cohorts of people exposed to professional, anthropogenic or medical irradiation, which causes the development of atherosclerosis of the vessels. It was shown that ionizing radiation is one of the promoters of the development of atherosclerosis.

Dose-rate effects in radiation biology and radiation protection.

Quantification of biological effects (cancer, other diseases, and cell damage) associated with exposure to ionising radiation has been a major issue for the International Commission on Radiological Protection (ICRP) since its foundation in 1928. While there is a wealth of information on the effects on human health for whole-body doses above approximately 100 mGy, the effects associated with doses below 100 mGy are still being investigated and debated intensively. The current radiological protection approach, proposed by ICRP for workers and the public, is largely based on risks obtained from high-dose and high-dose-rate studies, such as the Japanese Life Span Study on atomic bomb survivors. The risk coefficients obtained from these studies can be reduced by the dose and dose-rate effectiveness factor (DDREF) to account for the assumed lower effectiveness of low-dose and low-dose-rate exposures. The 2007 ICRP Recommendations continue to propose a value of 2 for DDREF, while other international organisations suggest either application of different values or abandonment of the factor. This paper summarises the current status of discussions, and highlights issues that are relevant to reassessing the magnitude and application of DDREF.

The Role of Polymorphisms of Key Genes of DNA Base Excision Repair in Terms of Lung Cancer Predisposition in "Mayak" Workers.

An association between polymorphic variants of key genes of base excision repair (BER) and lung cancer was studied in "Mayak" workers occupationally exposed to prolonged external y-rays and internal α-radiation from incorporated (239)Pu. The study was "case-control". The group of "cases" consists of 75 "Mayak" workers with the verified diagnosis of "lung cancer". At the moment of diagnosis the mean total absorbed dose from external y-rays to whole body was 1.19 Gy; the mean total absorbed dose from internal α-radiation due to incorporated (239)Pu in lung was 0.31 Gy. The group of "controls" includes "Mayak" workers matched by sex and birth year without lung cancer and other cancers during the study period (141 individuals). Increased lung cancer risk was revealed in workers-carriers of homozygous minor genotype of genes OGG] Ser326Cys (OR - 4.67, p = 0.007), APEI Asp148Glu (OR = 1.82, p = 0.063) and XRCC1 Gln399Arg (OR = 2.86, p = 0.026). Increased lung cancer risk was revealed in carriers of different pairwise combinations of minor genotypes of the studied genes of BER or in carriers of pairwise combinations with one homozygous minor mm-genotype and the other homozygous major ww genotype. Thus, OR of lung cancer in carriers of pairwise genotypes of mm genes OGG] Ser326Cys and APE] Asp 148Glu was 12.17.

Risk of mortality from circulatory diseases in Mayak workers cohort following occupational radiation exposure.

Mortality from circulatory diseases (CD) (ICD-9 codes 390-459) was studied in an extended Mayak worker cohort, which included 22,377 workers first employed at the Mayak Production Association in 1948-1982 and followed up to the end of 2008. The enlarged cohort and extended follow-up as compared to the previous analyses provided an increased number of deaths from CD and improved statistical power of this mortality study. The analyses were based on dose estimates provided by a new Mayak Worker Dosimetry System 2008 (MWDS-2008). For the first time in the study of non-cancer effects in this cohort quantitative smoking data (smoking index) were taken into account. A significant increasing trend for CD mortality with increasing dose from external gamma-rays was found after having adjusted for non-radiation factors; the excess relative risk per unit dose (ERR/Gy) was 0.05 (95% confidence interval (CI): >0, 0.11). Inclusion of an additional adjustment for dose from internal alpha-radiation to the liver resulted in a two-fold increase of ERR/Gy = 0.10 (95% CI: 0.02, 0.21). A significant increasing trend in CD mortality with increasing dose from internal alpha-radiation to the liver was observed (ERR/Gy = 0.27, 95% CI: 0.12, 0.48). However the ERR/Gy decreased and lost its significance after adjusting for dose from external gamma-rays. Results of the current study are in good agreement with risk estimates obtained for the Japanese LSS cohort as well as other studies of cohorts of nuclear workers.

[Molecular mechanisms of lung cancer development at its different stages in nuclear industry workers].

OBJECTIVE: to assess mutational events in exons 5, 7, and 8 of the p53 gene and to reveal mutant p53 protein in verified cases of morphologically altered (proliferative and precancerous changes, lung cancer) and histologically unaltered, lung tissues in workers exposed to occupational radiation. MATERIAL AND METHODS: The investigation used formalin-fixed paraffin-embedded unaltered and altered lung tissue blocks (FFPBs) obtained from the human radiobiological tissue repository. The shelf-life of FFPBs was 5-31 years. An immunohistochemical technique using mouse antibodies against p53 protein (<>, Denmark), stained with diaminobenzidine (DAB) chromogen, was employed to determine p53 protein. DNA was isolated from lung tissue FFPBs with QIAmp DNA FFPE Tissue Kit, (<>, USA). Polymerase chain reaction (PCR) was performed to amplify the p53 gene exons 5, 7, and 8 selected for examination, by applying the sequences of genes and primers, the specificity of which was checked using the online resource (http://www.ncbi.nlm.nih.gov/blast). PCR products were detected by temporal temperature gradient gel-electrophoresis and the Sanger sequencing method. The obtained DNA fragments were analyzed on a sequencer ABI Prism 3100 Genetic Analizer (<>, USA). Computer-aided DNA analysis was made using the BLAST program. A package of applied Statistica 6.0 programs was employed for statistical data processing. Results. Immunohistochemical analysis showed that mutant p53 protein was absent in the cells of unaltered lung tissue and the number of cells with mutant p53 protein increased in all the patients with proliferative and precancerous changes and lung cancer, suggesting p53 protein dysfunction. The total number of p53 gene mutations in exons 5, 7, and 8, if there were proliferative and precancerous lung tissue changes and lung cancer, were 25, 20, and 40%, respectively. All the found mutations were transversions (the substitution of purine for pyrimidine or, conversely), indicating the action of exogenous mutagens. CONCLUSION: The results of this investigation have confirmed other investigators' data showing that p53 gene mutations in lung cancer are observed in 40-70% of cases. The differences in the number of cases of altered lung tissue with mutations in the p53 gene (not more than 40%) and in those of p53 protein expression were found in 100%, suggesting the regulation of p53 gene function in the cell at multiple levels.

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.

[Possibility of DNA isolation from archived autopsy tissues for molecular genetic studies].

Optimal conditions were defined for DNA isolation from formalin-fixed and paraffin-embedded (FFPE) archived autopsy lung tissue slices. The quality of DNA preparations isolated from the FFPE archived slices was assessed and their suitability for further molecular genetic analysis estimated. DNA isolated from the FFPE slices stored less and more than 10 years was suitable for molecular genetic studies in 100 and 66.7% of cases, respectively.

[Role of gene polymorphisms of phase II of xenobiotic biotransformation from glutathione-S-transferase and N-acetyltransferase families in susceptibility to lung cancer among Mayak workers].

An association between polymorphous (allelic) gene variants of phase II of enzymatic xenobiotic biotransformation (EXB) of multigene families of glutathione-S-transferase (GSTs) GSTM1*0, GSTT1*0, GSTP1*B Ile105Val, and N-acetyltransferase (NAT) NAT2*6 590G>A, NAT2*5 481C>T, as well as lung cancer in Mayak workers exposed occupationally to prolonged external γ-rays and internal α-radiation from incorporated 239Pu was studied. Analysis of the population frequency of genotypes and alleles of the studied genes in the cohort of Mayak workers revealed their compliance with the Hardy-Weinberg principle and with the corresponding frequency in the European population. The study was based on the case-control method. A case-group consisted of 49 Mayal workers with a verified diagnosis of lung cancer. The mean total absorbed dose from external γ-rays at the moment of diagnostics was 1.03 Gy; the mean total absorbed dose from internal α-radiation from incorporated 239Pu to lung was 0.35 Gy. Control consisted of 172 Mayak workers matched by the year of birth, gender, and age at the moment of employment at one of the main facilities with no lung cancer registered within the study period. No increase in the relative risk of lung cancer (odds ratio, OR) was revealed among the individuals with deletion variants of genes GSTM1*0 and GSTT1*0 (pp genotype, complete absence of gene products) as compared to the individuals with ww or wp genotype, which was determined in total for these genes (normal or partly decreased gene activity). An increase in OR of lung cancer in 1.849 times (p = 0.239) and in 2.439 times (p = 0.075) was found in the carriers with a complete absence of the product of genes GSTP1*B and NAT2*6 590G>A, correspondingly (pp genotype). A statistically significant decrease in OR of lung cancer was found in the wp genotype carriers of gene GSTP1*B (OR = 0.50, p = 0.041). Three variants of paired combinations of gene alleles were established in the carriers with a statistically significant increase in OR of lung cancer (ww GSTP1*B + pp GSTM1*0; ww GSTP1*B + pp NAT2*6 590G>A; pp GSTP1*B + pp NAT2*5 481C>T), and one combination in the carriers with a statistically significant decrease in OR of lung cancer (wp GSTP1*B and ww +wp GSTT1*0).

[Cerebrovascular disease incidence in workers occupationally exposed to radiation over prolonged time periods].

OBJECTIVE: To estimate incidence rates for cerebrovascular diseases (CVD) in a cohort of workers occupationally exposed to radiation over prolonged time periods. MATERIAL AND METHODS: CVD incidence was estimated in a cohort of 22.377 workers of the nuclear facility "Mayak" Production Association over the follow-up period 1948-2008. Non standardized and standardized incidence rates were estimated. An indirect method of standardization was used for the estimates. RESULTS: As of 31/12/2008, 8.717 CVD cases (5.802 men and 2.915 women) were registered in the study cohort of workers. CVD incidence in the cohort was significantly associated with sex, age, smoking, alcohol consumption (in men) and arterial hypertension. CVD incidence was increased in workers exposed to external gamma-rays at total dose above 0.5 Gy and/or to internal alpha-radiation due to incorporated plutonium at total absorbed liver dose above 0.025 Gy. CONCLUSION: CVD incidence in the cohort of workers occupationally exposed to radiation over prolonged time periods was associated both with non-radiation and radiation factors.

[Prevalence of aortal atherosclerosis in workers underwent occupational irradiation].

The authors evaluated prevalence of aortal atherosclerosis in dependence on radiation and non-radiation factors in workers underwent occupational prolonged irradiation.The study included 22,377 workers of nuclear industry enterprise "Mayak", with verified diagnosis of aortal atherosclerosis. Up to 31th December 2008, a total of 1,840 aortal atherosclerosis cases were registered in the examinees group. Aortal atherosclerosis prevalence appeared to depend reliably on sex, age, smoking habit (in males), alcohol consumption (in males) and arterial hypertension. Findings are that aortal atherosclerosis prevalence was higher in males and females underwent external gamma-irradiation of total dose over 0.5 Gy, in males and females underwent internal alpha-irradiation from incorporated plutonium of total absorbed radiation dose in liver over 0.025 Gy. Thus, aortal atherosclerosis prevalence in workers underwent occupational irradiation de- pended both on radiational and non-radiational factors.

[Analysis of genome instability in offspring of "Mayak" workers families: minisatellite CEB1].

Genome instability transmission in offspring was analyzed in order to evaluate the risk of delayed genetic effects of exposure in 95 family triplets in which only fathers experienced prolonged occupational radiation exposure. The mean total preconceptive absorbed dose (TPAD) of external gamma radiation in the paternal gonads was 1.65 ± 0.08 Gy (dose range of 0.57-5.70 Gy), and the mean TPAD of internal alpha radiation from incorporated plutonium-239 in.the gonads was 0.0015 ± 0.0003 Gy (dose range 0.000-0.015 Gy). The control group consisted of 50 family triplets in which parents were not occupationally exposed. The mutation process was studied using PCR based on hypervariable minisatellite marker CEB 1 (chromosome 2, 2q37.3). The paternal type of inheritance of mutations for minisatellite CEB 1 was found in 80% of cases. The analysis revealed a statistically significant increase in minisatellite CEB1 mutations in the common group of families in which fathers experienced prolonged occupational radiation exposure and in the group of families in which fathers were exposed to radiation in a dosage range of 0.5-1.0 Gy as compared to the control, reaching a significance level of p = 0.109 and p = 0.058, respectively. The dose threshold of mutation detection in the off-spring of Mayak PA workers was estimated.

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 ancestral genotypes of the genes of xenobiotics biotransformation in susceptibility to lung cancer among Mayak workers].

An association between polymorphous (allelic) variants of genes of the 1st Phase of enzymatic xenobiotic biotransformation (EXB) in the superfamily of cytochromes P450 gene CYP1A1 * 2A (ml polymorphism), CYP1A1 * 2C (m2 polymorphism), gene CYP2E1 * 6 (C polymorphism), and between polymorphous vari- ants of gene of the 2nd EXB Phase of mircosomal epoxide hydrolase mEPOX Tyr113His (EH3 polymor- phism), and mEPOXHis139Arg (EH4 polymorphism) and lung cancer in Mayak workers with occupational prolonged exposure was studied. Analysis of population genotype frequency and alleles of genes CYP1A1 * 2A, CYP1A1 * 2C, CYP2E1 * 6, mEPOX Tyr113His, and mEPOXHis139Arg was conducted in the group of Mayak workers (289 individuals). The study has shown their compliance with the Hardy-Weinberg equilibrium, and correspondence of the genotype frequency to their frequency in European population. The study was per- formed using case-control method. Case-group consisted of 49 Mayak workers with verified diagnosis of lung cancer. Control-group consisted of 172 Mayak workers without lung cancer registered at the moment of the research. There was an increasing trend in odds ratio (OR) of lung cancer among homozygous carriers of the mutation in pp gene CYP1A1 * 2A, heterozygous carriers of the mutation in wp gene mEPOX Tyr113His and homozygous carriers ofww gene CYP2E1 * 6; also, there was a decreasing trend in OR among heterozy- gous carriers of wp gene CYP2E1 * 6. Two variants of pair allelic combinations of genes (genotypes ww CYP1A1 * 2A/genotype wp mEPOX Tyr113His, and genotype ww CYP2E1 * 6/genotype wp mEPOX Tyr113His) were revealed, which carriers had a statistically significant increase in the odds ratio of lung can- cer. With regard to these variants of genotype combinations, OR of lung cancer was 2.01 (CI 95%: 1.04-3.91) and 2.09 (CI 95%: 1.08-4.03), correspondingly.

[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.