Relationship between follow-up periods and the low-dose ranges with statistically significant radiation-induced risk of all solid cancers in the Russian cohort of Chernobyl emergency workers.

Radiation-induced risks for all solid cancer incidence and mortality were studied in the cohort of Russian Chernobyl emergency workers. The cohort included 69,440 persons with documented individual radiation dose accrued over the time of working in the Chernobyl zone. The mean age at entry into the zone of recovery operations was 33.9 years and accumulated radiation dose was 132.9 mGy. A total of 6981 solid cancer incident cases and 4272 deaths occurred in this cohort from 1992 to 2017. Three follow-up periods were studied: 1992-2009, 1992-2013, and 1992-2017. For each follow-up period, the lowest dose range with statistically significant (p < 0.05) radiation-induced risk of all solid cancer incidence and mortality were obtained. For the incidence of all solid cancer during the follow-up period 1992-2009, this lowest dose range was estimated to be 0-250 mGy with an excess relative risk per dose of ERR Gy-1 = 0.51 and 95% confidence interval (CI) (0.02; 1.05) Gy-1. For the period 1992-2013, the lowest dose range was 0-175 mGy with ERR Gy-1 = 0.85 (95% CI 0.03; 1.78), while for the whole follow-up period 1992-2017, it was 0-175 mGy with ERR Gy-1 = 0.81 (95% CI 0.08; 1.62). For mortality from all solid cancers during the follow-up period 1992-2009, the lowest dose range with statistically significant radiation-induced risk was estimated to be 0-225 mGy with ERR Gy-1 = 1.07 (95% CI 0.31; 0.97). For the period 1992-2013, the lowest dose range was 0-225 mGy with ERR Gy-1 = 0.86 (95% CI 0.23; 1.58), while for the whole follow-up period 1992-2017, the lowest dose range was 0-200 mGy with ERR Gy-1 = 0.82 (95% CI 0.10; 1.65). Thus, it was found that the minimal level of significant exposure (Dmin), for which a statistically significant radiation-induced risk of all solid cancers was obtained for Russian emergency workers (with individual doses of 0 - Dmin), decreases with increasing duration of cohort observation, both for cancer incidence and mortality.

CLINICAL AND DOSIMETRIC INFORMATION TO SUPPORT LONG-TERM COHORT STUDY OF CHERNOBYL CLEAN-UP WORKERS IN RUSSIA.

The article describes the activities of the Russian National Radiation-Epidemiological Registry (NRER) as the unified federal information system for research and management of individual medical and dosimetry data of people exposed to radiation as a result of the Chernobyl accident and other radiological events. The NRER was created for long-term registration of lifetime changes in the health status of the registered people. We present medical and dosimetry data management process, which is carried out in compliance with approved protocols. The scope and content of the information to be collected from external resources are defined in the documents approved by the Russian Ministry of Health. As of 2017 reporting year, the NRER contains medical and dosimetry information on 205 044 clean-up workers of the Chernobyl accident (liquidators), collected during the follow-up period from 1986 to 2016. Using special software for management of data from long-term studies of the Russian cohort of Chernobyl liquidators NRER ensures high quality of radiation-epidemiological information. The results of research activities of the NRER make great contribution to understanding biological and health effects of low-level radiation, molecular mechanisms of the effects, development of actions to early diagnostic of radiation-related diseases to respond to the needs of the affected population while minimizing unnecessary anxiety, improvement of targeting treatments delivery to exposed people at high risk, development of measures to reduce health risks from medical radiological procedures. During the post-Chernobyl period, new methods for estimating radiation doses were developed, some of them can be used for express estimation of radiation dose in the event of radiological emergency.

Radiation Risk of Cardiovascular Diseases in the Cohort of Russian Emergency Workers of the Chernobyl Accident.

This paper continues a series of publications that analyze the impact of radiation on incidence of circulatory system diseases in the cohort of Russian recovery operation workers (liquidators) and presents the results of the analysis of cardiovascular disease (CVD) incidence. The studied cohort consists of 53,772 liquidators who arrived in the Chernobyl accident zone within the first year after the accident (26 April 1986 to 26 April 1987). The individual doses varied from 0.0001 Gy to 1.42 Gy, and the mean external whole body dose in the cohort was 0.161 Gy. A total of 27,456 cases of CVD were diagnosed during the follow-up period 1986-2012 as a result of annual health examinations. A Poisson regression model was applied to estimate radiation risks and other risk factors associated with CVD. The following factors were identified as risk factors for CVD: the dose, duration of the liquidators' work in the Chernobyl zone, and concomitant diseases (diabetes mellitus, hypertension, overweight, and alcohol dependence). The baseline incidence of CVD is statistically significantly (p < 0.001) associated with all studied concomitant diseases. The incidence of CVD has revealed a statistically significant dose response with the lack of a latent period and with the average ERR Gy = 0.47, 95% CI = 0.31, 0.63, p < 0.001. Radiation risks of CVD statistically significantly (p = 0.01) varied with the duration of liquidators' stay in the Chernobyl zone; for those who stayed in the Chernobyl zone less than 6 wk, ERR/Gy = 0.80, 95% CI = 0.53; 1.08, p < 0.001.

Radiation-epidemiological Study of Cerebrovascular Diseases in the Cohort of Russian Recovery Operation Workers of the Chernobyl Accident.

The paper presents an analysis of the incidence of cerebrovascular diseases (CeVD) in the cohort of Russian workers involved in recovery tasks after the Chernobyl accident. The studied cohort consists of 53,772 recovery operation workers (liquidators) who arrived in the zone of the Chernobyl accident within the first year after this accident (26 April 1986-26 April 1987). The mean external whole body dose in the cohort was 0.161 Gy, while individual doses varied from 0.0001 Gy to 1.42 Gy. During the follow-up period 1986-2012, a total of 23,264 cases of CeVD were diagnosed as a result of annual health examinations. A Poisson regression model was applied for estimation of radiation risks and for an assessment of other risk factors of CeVD. The following factors were considered as risk factors for CeVD: the dose, duration of the liquidators' work in the Chernobyl zone, and the concomitant diseases (hypertension, ischemic heart disease, atherosclerosis, and diabetes). The baseline incidence of CeVD is statistically significantly (p < 0.001) associated with all studied concomitant diseases. The incidence of CeVD has revealed a statistically significant dose response with the lack of a latent period and with the average ERR/Gy = 0.45, 95% CI: (0.28, 0.62), p < 0.001. Radiation risks of CeVD statistically significantly (p = 0.03) varied with the duration of liquidators' stay in the Chernobyl zone; for those who stayed in the Chernobyl zone less than 6 wk, ERR/Gy = 0.64, 95% CI = (0.38; 0.93), p < 0.001. Among studied concomitant diseases, diabetes mellitus statistically significantly (p = 0.002) increases the radiation risk of CeVD: for liquidators with diagnosed diabetes, ERR/Gy = 1.29.

Incidence and mortality of solid cancer among emergency workers of the Chernobyl accident: assessment of radiation risks for the follow-up period of 1992-2009.

This paper presents the results of a retrospective cohort study of cancer incidence and mortality among emergency workers of the Chernobyl accident, for the follow-up period 1992-2009. The cohort selected for analysis consists of 67,568 emergency workers who worked in the Chernobyl exclusion zone in 1986-1987. External radiation whole-body absorbed dose varied from 0.0001 gray (Gy) to 1.24 Gy, with a median of 0.102 Gy. Over the follow-up period 1992-2009, a total of 4,002 solid cancers of different sites were identified as the result of annual compulsory health examination, and a total of 2,442 deaths from all solid cancers in the study cohort were reported. Poisson regression was applied for the analysis of cancer incidence and mortality. The analysis of the standardized incidence ratio (SIR) has shown a statistically significant increase in cancer incidence in the cohort as compared with baseline cancer incidence among males of Russia. The average excess over the entire follow-up period is 18 % [SIR = 1.18, 95 % confidence interval (CI) 1.15; 1.22]. In contrast, however, no increase in the mortality from all cancers among the emergency workers as compared to the baseline mortality in Russian men was found. Values of excess relative risk of cancer incidence and mortality per 1 Gy (ERR Gy(-1)) are 0.47 (95 % CI 0.03; 0.96, p value = 0.034) and 0.58 (95 % CI 0.002; 1.25, p value = 0.049), respectively. These values are statistically significant.

Estimating the lifetime risk of cancer associated with multiple CT scans.

Multiple CT scans are often done on the same patient resulting in an increased risk of cancer. Prior publications have estimated risks on a population basis and often using an effective dose. Simply adding up the risks from single scans does not correctly account for the survival function. A methodology for estimating personal radiation risks attributed to multiple CT imaging using organ doses is presented in this article. The estimated magnitude of the attributable risk fraction for the possible development of radiation-induced cancer indicates the necessity for strong clinical justification when ordering multiple CT scans.

Estimation of risk from medical radiation exposure based on effective and organ dose: how much difference is there?

The authors compare radiation risks of potential cancer following diagnostic radiation exposure evaluated with the use of organ and effective doses. Lifetime attributable risk values of CT scanning are estimated with the use of ICRP (Publication 103) risk models and Russian national medical statistics data. For populations under the age of 50, the risk evaluated using organ doses usually differs from that using effective doses by <30 %. In older populations, the difference can be up to a factor of 3. Calculated values of lifetime attributable cancer risk for particular organs are presented as well.

Formation of potential radiation risk groups to render timely targeted medical care: lessons of Chernobyl.

The paper discusses technology for establishing potential cancer risk groups, based on methods of molecular and radiation epidemiology. Assay of gene mutations at the T-cell receptor (TCR) locus as the method of molecular epidemiology was used for measuring the frequency of TCR-mutations in 320 nuclear workers of the Institute of Physics and Power Engineering (IPPE). The method of radiation epidemiology was applied to the estimation of attributable risk fraction (ARF) for solid cancers in these groups. The main estimates of radiation risk after the Chernobyl accident are in close agreement with the International Commission on Radiological Protection (ICRP) Publication, 103 models published in 2007. In nuclear workers of the IPPE with ARF ≥ 10%, the increased level of TCR-mutations occurs more often (risk ratio=9.7; 95% CI: 2.9; 32.1).

Radiation-epidemiological studies of thyroid cancer incidence in Russia after the Chernobyl accident (estimation of radiation risks, 1991-2008 follow-up period).

This study presents an analysis of the thyroid cancer incidence in the population of the most contaminated territories of Bryansk, Kaluga, Oryol and Tula oblasts affected by the Chernobyl accident. The follow-up period is 1991-2008, and the cohort size is 309 130 people. For that period 978 thyroid cancer cases were detected. The excess relative risk per 1 Gy (ERR/Gy) is found to be statistically significant for children and adolescents (0-17 y of age) at the time of the Chernobyl accident (ERR/Gy=3.22; 95 % confidence interval (1.56; 5.81). In boys, the ERR/Gy was higher than in girls -6.54 and 2.24, respectively. A statistically significant decrease in ERR/Gy with time since exposure, by a factor of 0.37 per 10 y, was observed for the whole cohort and for boys separately, but not for girls. No radiation risks of a thyroid cancer among people of 18 y of age at exposure and older were found.

Leukemia incidence in the Russian cohort of Chernobyl emergency workers.

Of all potentially radiogenic cancers, leukemia, a type of cancer of the blood, has the highest risk attributable to ionizing radiation. Despite this, the quantitative estimation of radiation risk of a leukemia demands studying very large exposed cohorts, because of the very low level of this disease in unexposed populations and because of the tendency for its radiation risk to decrease with time. At present, the Japanese cohort of atomic bomb survivors is still the primary source of data that allows analysis of radiation-induced leukemia and the underlying dose-response relationship. The second large cohort that would allow to study radiation-induced leukemia is comprised of individuals who were exposed due to the accident of the Chernobyl nuclear power plant in 1986. The objective of the present study was to estimate radiation risks of leukemia incidence among the Russian cohort of Chernobyl emergency workers, for different time periods after the accident. Twenty-five years after the Chernobyl accident and based on the results of the present study, one can conclude that the radiation risk of leukemia incidence derived from the Russian cohort of Chernobyl emergency workers is similar to that derived from the cohort of atomic bomb survivors: The time-averaged excess relative risk per Gray (ERR Gy(-1)) equals 4.98 for the Russian cohort and 3.9 for the life span study (LSS) cohort; excess absolute risk decreases with time after exposure at an annual rate of 9% for the Russian cohort, and of 6.5% for the LSS cohort. Thus, the excess in risk of leukemia incidence in a population due to a single exposure is restricted in time after exposure by the period of about 15 years.

[Mortality among the liquidators of the Chernobyl accident: dose dependences and groups of the potential risk].

Dynamics of the mortality and the mortality radiation risks among male emergency workers of 1986-1987 years of entrance to the Chernobyl zone is analyzed. The average dose of external gamma-exposure for this cohort equals 128 mGy. The size of the cohort at the beginning of the follow-up in 1992 was 47820 persons. For the follow-up period 1992-2006 statistically significant radiation risks of death rates have been estimated: for the mortality from all causes, the excess relative risk per Gy (ERR/Gy) equals 0.42 with 95% confidence interval (95% CI) (0.14-0.72); for the mortality from solid cancers ERR/Gy = 0.74, 95% CI (0.03-1.76); and for the mortality from the circulatory system diseases ERR/Gy = 1.01, 95% CI (0.51-1.57). Based on these estimates the risk groups were ranked among all Russian emergency workers (160 thousand persons): the group of the potential radiation risk with doses more than 150 mGy (33488 persons) and the group of the high radiation risk with doses more than 240 mGy (6054 persons).

[Investistigation of the role of heterogenety individual radiosensitivity in estimation of radiation indused ageing].

The influence of heterogeneity in individual radiosensitivity on estimation of ageing using survival curve is considered. Quadratic deviation of the rate of ageing from the true value in estimated by imitation modeling techniques. The Gompertz model for spontaneous mortality and gamma-frailty model for heterogeneity are used. Simulation performed at different values of radiation effect and heterogeneity variance. It is shown that inclusion heterogeneity in the model is not efficient for large values of heterogeneity variance. For moderate values of heterogeneity variance model with heterogeneity produces more accurate results in comparison with the model without heterogeneity.

Latent period in induction of radiogenic solid tumors in the cohort of emergency workers.

The paper presents estimates for the latent period of the induction of radiogenic solid cancers among Chernobyl emergency workers (males) living in six central regions of Russia. The analysis is based on medical and dosimetry data gathered by the National Radiation and Epidemiological Registry over the time period from 1986 to 2005. The cohort includes 59,770 persons who stayed in the exposure zone (30-km zone around the Chernobyl nuclear power plant) in 1986-1987. There were 2,718 cases of solid tumors identified during the follow-up time in this cohort. The mean radiation dose in the cohort is 0.13 Gy. The radiation risk and latent period were estimated using the method of maximum likelihood. The excess relative risk per unit dose was found to be 0.96 (95% confidence interval (CI): 0.3-1.7) and the minimum latent period for induction of solid tumors is 4.0 years (95% CI: 3.3-4.9).

Risk of thyroid cancer among Chernobyl emergency workers of Russia.

The presented paper deals with the thyroid cancer incidence in selected cohorts of emergency workers of Russia. In 1986-2003, a total of 87 cases of thyroid cancer were observed. Based on these data, a statistically significant increase in thyroid cancer incidence was found above the reference level for the male population of Russia, corresponding to a standardized incidence rate (SIR) of SIR = 3.47 [95% confidence interval (CI): 2.80; 4.25]. The highest incidence rate (SIR = 6.62, 95% CI: 4.63; 9.09) was shown for those emergency workers who took part in the early recovery operations in April-July 1986. The estimated SIR value increases to 7.97 (95% CI: 5.24; 11.52) after allowing for a 10 years latent period of Chernobyl-related thyroid cancers. These results indicate that the exposure to incorporated (131)I was the major risk factor of thyroid cancer among Chernobyl emergency workers. No statistically significant relationship was found for the thyroid cancer incidence and external radiation dose.

[Thyroid cancer incidence among Chernobyl emergency workers: follow-up period 1986-2003].

A vast amount of research articles devoted to the increase in childhood thyroid cancer incidence in the most contaminated by radionuclides territories of Belarus, Russia and Ukraine affected by the Chernobyl accident were published recent years. However, the amount of research studies of thyroid cancer incidence among the Chernobyl emergency workers (liquidators) is quite scanty. In the article results of the study of thyroid cancer incidence in the cohort of the Chernobyl liquidators (103427 persons) residing in 6 administrative regions of Russia (North-West, Volgo-Vyatsky, Central-Chernozemny, Povolzhsky, North-Caucasus and Urals) are described and discussed. For the period 1986-2003 eighty seven cases of thyroid cancer were detected in the cohort. Statistically significant excess of the incidence among liquidators over baseline incidence, SIR = 3.39 (95% CI: 2.73; 4.16), among men of Russia has been found. The highest thyroid cancer incidence (SIR = 6.49) was registered among liquidators who had been involved in mitigation works during April-July 1986. At the same time no statistically significant relationship between the incidence rate and external radiation dose, ERR = 1.68 (95% CI: -0.95; 6.46), was detected.

[Cancer morbidity and mortality among the liquidators of the Chernobyl accident: estimation of radiation risks].

The work focuses on the results of the analysis of the cancer incidence among the Chernobyl emergency workers residing in Russia during 1991-2001. The analysis is based on the data for the cohort of male emergency workers from 6 regions of Russia including 55718 persons with documented external radiation doses in the range of 0.001-0.3 Gy who worked within the 30-km zone in 1986-1987. The mean age at exposure for these persons was 34.8 years old and the mean external radiation dose 0.13 Gy. In this cohort 1370 cases of solid cancer were diagnosed. Three follow-up periods were considered: 1991-1995, 1996-2001 and 1991-2001. The second follow-up period was chosen to allow for a minimum latency period of 10 years. Risk assessments were performed for two control groups: the first control group ("external") represented incidence rates for corresponding ages in Russia in general and the second control group ("internal") consisted of emergency workers. The estimated standardized incidence ratio (SIR) is in good agreement with that of the control within 95% CI. The values of the excess relative risk per unit dose 1 Gy (ERR/Gy) for solid malignant neoplasms have been estimated to be 0.33 (95% CI: -0.39, 1.22) (internal control) for the follow-up period 1991-2001 and 0.19 (95% CI: -0.66, 1.27) for 1996-2001. The analysis of cancer morbidity was carried out for the cohort of 29003 emergency workers who took part in liquidation of the consequences of the Chernobyl accident from 26 April 1986 to 25 April 1987. It was shown that the excess relative risk of cancer deaths per unit dose 1 Sv (ERR/Sv) is equal to 1.52 (95% CI: 0.20, 2.85).