Comparing the risk of mortality from solid cancer after radiation incidents and occupational radiation exposure

The purpose of the study is to compare the excess relative risk (ERR per 1 Sv) of solid cancer mortality in acute - catastrophic or emergency, and occupational - fractionated or chronic exposure. Materials and research methods. A maintained database (database of sources) on nuclear workers from about 40 countries, on the basis of it a combined data analysis was carried out to determine the integral ERR value per 1 Gy for cancer mortality for comparison with parameters of cohorts exposed to catastrophic and emergency exposure: the LSS cohort victims of the atomic bombings in Japan, residents of the Techa River (radioactive contamination due to emissions from the Mayak plant) and Russian liquidators of the Chernobyl accident. Results. Comparison of the ERR per 1 Sv for cancer mortality for workers in the global nuclear industry (combining analysis of data from 37 studies) with the parameters of the LSS cohort, residents on the Techa River and liquidators of the Chernobyl accident showed the absence of logical and principial differences, and the risks for the last two cohorts were the highest. Although the data obtained partly confirm the approach of recent years by the United Nations Scientific Committee on the Effects of Atomic Radiation, according to which the carcinogenic effects of acute, accidental, and fractionated or chronic radiation exposure do not depend on the dose rate factor (DDREF), nevertheless, taking into account biological mechanisms and data radiobiological experiments, this issue cannot be considered unambiguously resolved. Conclusion. Based on the ERR per 1 Sv, the average external dose, and the annual background cancer mortality in Russia and the United States, the expected increase in cancer mortality for 100,000 nuclear workers will average 32-69 people over 10 years (0.032-0.069% of the group). Such risks, due to the many carcinogenic non-radiation factors of life and work, as well as fluctuations in the background value, cannot be taken into account in the practice of medicine and health care.

Breast cancer incidence risk in accidentally exposed persons of the Southern Urals

The objective of the paper is to assess the breast cancer incidence risk in the Ural cohort of accidentally exposed population. The cohort of people exposed in the Southern Urals on the Techa River and in the East Ural Radioactive Trace was created in 2018. This is the first time that breast cancer risk analysis in women in this cohort is being carried out. Over the period from 1956 to 2018, 337breast cancer cases and 741,533person-years at risk were reported in the female subcohort in the incidence catchment area. Mean accumulated dose to the mammary gland, calculated using the TRDS-2016 dosimetry system, was 46 mGy, the maximum dose was 1 Gy. Regression analysis was performed using the EPICURE software package. Statistical significance with 95% probability was assessed by the maximum likelihood method. As a result of the analysis, a statistically significant linear dependence of breast cancer parameters on the dose was obtained. Excess relative risk for the follow-up period from 1956 through 2018 for members of the female subcohort with a 5-year latency period was 2.39 / Gy. The paper also discusses the impact of available for analyses non-radiation factors on both baseline rates of breast cancer incidence and those associated with radiation exposure. These results do not contradict those obtained in the previous study in the Techa River Cohort separately, and in the Japanese L SS cohort of atomic bomb survivors.

Comparison of the Risk of Mortality from Solid Cancers after Radiation Incidents and Occupational Exposures

The purpose of the study was to compare the excess relative risk of mortality (ERR per 1 Sv) from solid cancers during acute — catastrophic or accidental and occupational, fractionated or chronic — exposure. Study materials and methods. Materials of the study: maintained database (source database) on nuclear industry workers from about 40 countries, based on which a pooled analysis of data was conducted to determine the integral value of ERR per 1 Gy for mortality from solid cancers; indicators of cohorts exposed to catastrophic and accidental radiation: the cohort LSS victims of the atomic bombings in Japan; residents of the Techa River — radioactive contamination resulting from releases from "Mayak" production association; Russian liquidators of the Chernobyl nuclear accident. Study results and analysis. Comparison of the ERR of 1 Sv deaths from solid cancers for workers in the global nuclear industry (pooling analysis of data from 37 studies) with those of the LSS cohort; Techa River residents and Chernobyl accident liquidators showed no logical and principled differences, with the risks for the latter two cohorts being the highest. Although the findings partly support the approach of the UN Scientific Committee on the Effects of Atomic Radiation that the carcinogenic effects of acute (catastrophic or accidental) and occupational (fractionated or chronic) radiation exposure are independent of the dose rate factor (DDREF), this issue cannot be considered unequivocally resolved, given the biological mechanisms and radiobiological experimental data. Based on the ERR per 1 Sv, the average external dose, and the annual background cancer mortality rates in Russia and the United States, the expected cancer mortality increase for 100,000 workers in the nuclear industry would be an average of 32-69 people over 10 years — 0.032-0.069% of the group. Such risks, due to multiple carcinogenic non-radiation factors of life and work, as well as fluctuating background values, cannot be taken into account in the practice of disaster medicine and public health.

BCL-2, CDKN1A and ATM gene methylation in chronically exposed individuals

DNA methylation is the most common epigenetic modification, caused by ionizing radiation. There may be both hypermethylation, which suppresses transcription of gene promoter regions, and hypomethylation, resulting in gene activation. Both mechanisms may be involved in carcinogenesis. The study was aimed to assess methylation status of CpG islands in the protective system BCL-2, CDKN1A and ATM gene promoters in the peripheral blood cells of the chronically exposed individuals, living in the villages, located along the Techa River, over a long-term period. Methylation of BCL-2, CDKN1A and ATM gene promoter regions in 68 residents of the villages, located along the Techa River (Chelyabinsk region), was assessed by the real-time methylation-specific PCR. The group of exposed individuals included 54 people with accumulated dose to red bone marrow within the range of 0.09–3.51 Gy. The comparison group included 14 people, living in similar economic and social environment, with the dose to red bone marrow, accumulated during the whole life, not exceeding 70 mGy. The pilot study of exposed individuals over a long period of time after chronic low-dose radiation exposure revealed no significant changes in methylation levels of CpG islands in the CDKN1A, BCL-2, ATM gene promoter regions compared to the comparison group. None were revealed in the dose subgroups “87–994 mGy” and “over 1000 mGy”.

Radiogenic risk of solid cancer incidence in persons exposed to radiation in childhood in the Southern Urals

The aim of this work is to assess the radiogenic risk of solid cancers incidence in the members of the Urals Childhood Exposure Cohort. The cohort includes people exposed under 20 years of age as a result of two radiation accidents at the Mayak Production Association in the Southern Urals (discharges of radioactive waste into the Techa River and the formation of the East Ural radioactive trace). The number of the cohort for solid cancer incidence analysis is 31,578 individuals. All the members were postnatally exposed and some of them – in-utero. Some of their parents were exposed before conception. 2,018 solid cancers were registered on the incidence catchment area during the period 1956-2018, the total amount of person years was 818,083. The analysis was carried out by the Poisson regression method with a simple parametric excess relative risk model. 95% confidence intervals were estimated with maximum likelihood approach. Only a postnatal dose was used in the first solid cancer incidence analysis of this cohort members with due account for preconception exposure of parents. TRDS-2016 mean postnatal dose accumulated over the entire follow-up period in the stomach of cohort members was 0.047 Gy. The analysis showed linear dependence of solid cancer incidence excess relative risk on postnatal dose. Excess relative risk was 0.66/Gy, р=0.006 with a five-year latency period. While estimating excess relative risk in different age groups at the beginning of exposure, a significant risk was present only in the age group under 1 year and amounted to 2.16/Gy; р<0.02 at the onset of exposure. The present results are in agreement with the results of the solid cancer incidence risk analysis both in the Techa River Cohort of exposed In-Utero where a statistically significant excess relative risk from a postnatal dose was revealed, and with the results of risk analysis in the Japanese cohort of people exposed in-utero and in early childhood.

Solid Cancer Incidence Risk among the Population Exposed in the East Urals Radioactive Trace over 1957–2014

Purpose: Assessment of solid cancer incidence risk in the cohort of exposed population on the territory of the East Urals radioactive trace over the period of follow-up from 1957 to 2014 with the use of the individual doses provided by the latest TRDS dosimetry system. Material and methods: The explosion of the liquid radioactive waste storage tank at the «Mayak» Production Association on 29 September 1957 led to the pollution of the territories of the Chelyabinsk and Sverdlovsk Regions and the formation of the EURT, and the population residing on its territory was subjected to protracted chronic external and internal exposure. The analyzed cohort includes 21,384 people, 2,055 of whom received additional radiation before the 1957 accident due to residing in one of the Techa River settlements. The mean dose to the stomach for the members of the EURT cohort was 36 mGy, the maximum — 1.13 Gy. The analysis was performed using the DATAB and AMFIT programs (statistical software package EPICURE). A simple parametric model of excess relative risk (ERR) was used. Statistical significance and confidence intervals were obtained using the maximum likelihood method. Results: As a result of the analysis of the solid cancer incidence risk in the EURT cohort during the 57-year follow-up period using the linear model and the 5-year latent period, a statistically significant ERR was obtained which equals to 0.052 / 100 mGy (95 % CI 0.01–0.10, p = 0.02) in the entire EURT cohort. When the group of people additionally exposed on the Techa River before the 1957 accident was excluded from the cohort, the risk became insignificant. No significant modification of the dose dependence by non-radiation factors was revealed. The obtained results are compared well with the previous studies of the exposed population in the Southern Urals which were conducted in the Urals Research Center for Radiation Medicine, as well as in the world, devoted to the study of the effects of radiation exposure on population.

Apoptosis of Lymphocytes and Polymorphisms of Apoptosis Regulation Genes in Individuals Exposed to Chronic Radiation Exposure

Purpose: Study the apoptotic death of peripheral blood lymphocytes in long-term period in persons exposed to chronic radiation exposure, and analysis of association of the polymorphic regions rs4645878, rs2279115, rs28362491, rs664677, rs1042522, rs1801270, rs2279744 of the BAX, BCL2, NFkB, ATM, TP53, CDKN1A, MDM2 genes with apoptotic lymphocytes frequency in residents of the coastal villages of the Techa River. Material and methods: The study of apoptosis and genotyping was conducted in 390 persons exposed to chronic radiation exposure as a result of Mayak PA radioactive waste releases into the Techa–Iset–Tobol river system. The early stage of apoptosis was assessed on a flow cytometer by the presence of phosphatidylserine on the surface of the cell membranes using the Annexin V Apoptosis Detection Kit I and the late stage of apoptosis using the TUNEL method. Real-time PCR genotyping was performed of allelic variations of rs4645878, rs2279115, rs28362491, rs664677, rs1042522, rs1801270, rs2279744 of BAX, BCL2, NFkB, ATM, TP53, CDKN1A, MDM2 genes in a group of irradiated individuals. Results: The number of cells at the early stage of apoptosis is statistically significantly increased in individuals whose irradiation began during the period of intrauterine development and continued in the postnatal period compared to individuals exposed only in the postnatal period. At the same time, the number of lymphocytes at the stage of DNA fragmentation in the group irradiated in utero is lower than in the group irradiated postnatally and non-irradiated individuals. Also, a weak negative correlation between intrauterine doses of RBM irradiation and the doses of thymus and peripheral lymphoid organs with the number of cells in the late stage of apoptosis in individuals irradiated in utero. The influence of allelic variation rs4645878 of the BAX gene was established on the number of lymphocytes at the early stage of apoptosis in residents of coastal villages of the Techa River. A statistically significant decrease in the number of cells at an early stage of apoptosis is observed in C/C genotype carriers according to the allelic variation rs4645878 of the BAX gene compared with carriers of the T/T and T/C genotypes. Conclusion: Residents of coastal villages of the Techa River exposed to radiation during the period of prenatal development, there are differences in the frequency of apoptotic death of peripheral blood lymphocytes compared with non-irradiated persons and persons who were irradiated in the postnatal period. SNPs of apoptosis-regulating genes can modify the response of blood lymphocytes to radiation in a wide range of doses RBM.