Descriptive characteristics of occupational exposures and medical follow-up in the cohort of workers of the Siberian Group of Chemical Enterprises in Seversk, Russia.

PURPOSE: To date, only a few studies have examined long-term health risks of exposures in the uranium processing industry and reported contradictory results, necessitating further research in this area. This is the first description of a cohort of ∼65,000 uranium processing workers (20.6% women) of the Siberian Group of Chemical Enterprises (SGCE) in Seversk, Russia, first employed during 1950-2010. METHODS: SGCE is one of the largest and oldest uranium processing complexes in the world. SGCE workers at the Radiochemical, Plutonium, Sublimate and Enrichment plants were exposed to a combination of internal and external radiation, while workers at the Support Facility were primarily exposed to non-radiation factors. RESULTS: Mean cumulative gamma-ray dose based on individual external dosimetry was 28.3 millisievert. About 4,000 workers have individual biophysical survey data that could be used for estimation of organ doses from uranium. SGCE workers were followed up for mortality and cancer incidence during 1950-2013 (vital status known for 80.8% of workers). The SGCE computerized database contains information on the results of regular medical examinations, and on smoking, alcohol and other individual characteristics. CONCLUSIONS: The SGCE cohort is uniquely suited to examine long-term health risks of exposures to gamma-radiation and long-lived radionuclides in uranium processing workers.

Association between TP53 gene ARG72PRO polymorphism and chromosome aberrations in human cancers.

It is well known that the TP53 gene considerably influences on DNA repair processes. Polymorphisms in the TP53 gene, particularly the well-known Arg72Pro in codon 72 of exon 4 (Ex4+119 G>C; rs1042522), can modify the functionality of the p53 protein and activation of DNA repair. Actually, polymorphic variants Arg and Pro were found to have different properties of regulation of TP53-dependent DNA repair target genes, that can effect various levels of chromosome aberrations in cancer patients with these genotypes. Here, we studied frequency of chromatid breaks (CB), chromosome-type aberrations (CTA) and aberrant cells (AC) in cancer patients (n = 102) with various Arg72Pro genotypes. It was shown that the Arg variant of TP53 gene is associated with high frequency of AC and chromatid breaks. That is Arg/Arg carriers have more different chromosome aberrations in comparison to individuals with Arg/Pro and Pro/Pro genotypes (P < 0.05). Conversely, the lowest level of AC and chromatid breaks were detected in cancer patients with the Pro/Pro genotype. A completely unexpected result was that women with Arg/Arg genotype had the most high frequency of CB and AC in comparison to Arg/Pro and Pro/Pro women carriers (P < 0.001). In the group of male patients we did not show any differences in chromosome aberrations between carriers of Arg72Pro genotypes. In conclusion, the TP53 gene Arg72Pro polymorphism appreciably influence on occurrence of chromosome aberrations in cancer.

Molecular Relationships between Bronchial Asthma and Hypertension as Comorbid Diseases.

Comorbidity, a co-incidence of several disorders in an individual, is a common phenomenon. Their development is governed by multiple factors, including genetic variation. The current study was set up to look at associations between isolated and comorbid diseases of bronchial asthma and hypertension, on one hand, and single nucleotide polymorphisms associated with regulation of gene expression (eQTL), on the other hand. A total of 96 eQTL SNPs were genotyped in 587 Russian individuals. Bronchial asthma alone was found to be associated with rs1927914 (TLR4), rs1928298 (intergenic variant), and rs1980616 (SERPINA1); hypertension alone was found to be associated with rs11065987 (intergenic variant); rs2284033 (IL2RB), rs11191582 (NT5C2), and rs11669386 (CARD8); comorbidity between asthma and hypertension was found to be associated with rs1010461 (ANG/RNASE4), rs7038716, rs7026297 (LOC105376244), rs7025144 (intergenic variant), and rs2022318 (intergenic variant). The results suggest that genetic background of comorbidity of asthma and hypertension is different from genetic backgrounds of both diseases manifesting isolated.

The bank of biological samples representing individuals exposed to long-term ionizing radiation at various doses.

Collection and storage of biological specimens in biobanks aims to obtain and preserve samples of different kinds for biological and medical studies. Here we present a description of the Bank of Biological Materials (BBM) housed by the Seversk Biophysical Research Centre (SBRC; Seversk, Russia). The main goal of maintaining the BBM is to collect and store biological samples suitable for genetic studies of people exposed to long-term ionizing radiation. Currently, the collection includes 19,194 biological specimens obtained from 8105 donors, of whom 42.3% are diagnosed with malignant neoplasms, 28.7% are healthy residents of the city of Seversk, 18.8% are healthy employees of the Siberian Group of Chemical Enterprises (SGCE), and 10.2% are patients diagnosed with acute myocardial infarction. The donors were enrolled using the Regional Medical and Dosimetric Register database created by the SBRC. For each donor, DNA specimens were extracted from peripheral blood and tissues and cell suspensions for cytogenetic analysis were prepared routinely. The BBM's unique collection is suitable primarily for studies of individual radiosensitivity of humans (IRH), and genetic aspects of the pathophysiology of common human diseases, especially in populations exposed to long-term low-dose ionizing radiation.

The risk of acute myocardial infarction and arterial hypertension in a cohort of male employees of a Siberian Group of Chemical Enterprises exposed to long-term irradiation.

During the period from 1998 to 2007, a prospective cohort study of acute myocardial infarction morbidity cases as well as a "case-control" study of arterial hypertension was carried out. The risk of acute myocardial infarction was assessed as well as arterial hypertension; the dose-response relationship and the role of radiation in the mechanism of acute myocardial infarction as well as arterial hypertension development were studied. As a result of this study, a statistically significant increased risk of acute myocardial infarction among the male staff at the Siberian Group of Chemical Enterprises [standardized relative risk = 1.16 (1.04; 1.29)] exposed to external irradiation in comparison with employees unexposed to ionizing radiation was observed. A significant increase in the risk of acute myocardial infarction was observed at external radiation dose accumulation of more than 300 mSv [standardized relative risk = 1.46 (1.09; 1.91)]. The increase in arterial hypertension risk has been established among the analyzed group of employees exposed to long-term irradiation in the absence of the linear dependence of risk, based on cumulative dose of external γ-irradiation [risk due to external radiation dose in the range of 7.3-21.3 mSv = 1.6 (0.96; 2.51) and in the range of external radiation dose 21.4-68.5 mSv = 1.7 (1.04; 2.67) for 68.6-864 mSv = 1.6 (1.01; 2.57)]. This led to the conclusion that radiation can act also as a factor that might potentiate the negative effects of the "traditional" risk factors in the pathogenesis of acute myocardial infarction and hypertension.