The effect of Chernobyl accident on the development of malignant diseases--situation after 20 years

The accident that occurred at the Chernobyl Nuclear Power Plant in 1986, released large quantities of radionuclides--among them radioiodine--into the atmosphere, thereby raising public concerns about its influence on thyroid structure and function, especially the development of malignancy. There were even reports about 700 deaths due to thyroid carcinoma in Russian Federation, Ukraine and Belarus, resulting from the accident. In this review we discussed the incidence of thyroid cancer in different parts of the world, especially in heavily contaminated countries, as Ukraine and Belarus, and the possible link between radioisotope activity in the thyroid and the development of malignancy. The study carried out in Minsk showed 40-fold increase of the incidence of thyroid cancer in the years 1986-1994, in comparison to the period 1977-1985. An increase of the incidence of thyroid cancer has generally been observed in many countries after the Chernobyl accident. We focused on the factors that may have an influence on this phenomenon, especially diagnostic tests, health care, social and environmental factors, like iodine level in water and soil. The results of molecular biology studies, e.g. RET translocation in carcinoma type RET/PTC1 in elderly and RET/PTC3 in children, and expression Ax1 and Gas6 in children were reviewed as well. We also mentioned other thyroid diseases, like nodular goitre, cysts, the disturbance of thyroid function and autoimmunity, possibly linked to the radiation after Chernobyl accident. Data obtained from the regions near Chernobyl showed no increased risk of other types of malignancy (leukaemia, Hodgkin's and non Hodgkin's lymphoma) in 1986-1996. In this article the epidemiology of thyroid diseases in Poland was also reviewed.     

Nuclear-power-plant accidents: thyroid cancer incidence and radiation-related health effects from the Chernobyl accident

Following the Chernobyl accident, enormous amounts of radioisotopes were released in the atmosphere and have contaminated surrounding populations in the absence of rapid protective countermeasures. The highest radiation doses were delivered to the thyroid gland, and the only direct consequence of radiation exposure observed among contaminated population is the increased incidence of thyroid cancers among subjects who were children in 1986 and who lived at that time in Belarus, Ukraine or Russia.     

Analysis of thyroid cancer data from the Ukraine after ’Chernobyl’ using a two-mutation carcinogenesis model

The thyroid cancer data of children in the northern regions of the Ukraine after the reactor accident at Chernobyl were combined with thyroid dose measurements in the same regions and analysed using a two- mutation carcinogenesis model. The best fit was obtained for radiation acting as an initiating agent, i.e. on the first mutation of the model. The observed relatively high increase of thyroid cancer incidence after 1990 in children exposed to radiation released after the reactor accident could be ascribed to the high thyroid doses and the relatively low background thyroid cancer incidence in children. The maximum annual incidence is predicted to occur fairly soon after the reactor accident, i.e. about 10 years. For adults, the predicted relative increase of annual thyroid cancers is much lower than for children younger than 20 years. The modelling results are used to derive risk estimates for radiation-induced thyroid cancer. These risk estimates are dependent on age at exposure, follow-up time and the background thyroid cancer incidence. The calculated excess absolute risk for a population of all ages is about one-third of that currently used by ICRP, but for children the calculated absolute risks are about a factor of 3 higher than derived in other epidemiological studies. The model results indicate that the excess absolute radiation risk per unit dose for children is about the same as or a little lower than that for adults. Received: 11 May 1999 / Accepted: 30 December 1999     

Post-Chornobyl thyroid cancers in Ukraine. Report 1: estimation of thyroid doses

About 1.8 EBq of 131I was released into the atmosphere during the Chornobyl accident that occurred in Ukraine on April 26, 1986. More than 10% of this activity was deposited on the territory of Ukraine. Beginning 4-5 years after the accident, an increase in the incidence of thyroid cancer among children, believed to be caused in part by exposure to 131I, has been observed in different regions of Ukraine. A three-level system of thyroid dose estimation was developed for the reconstruction of thyroid doses from 131I for the entire population of Ukrainian children aged 1 to 18 at the time of accident: (1) At the first level, individual doses were estimated for the approximately 99,000 children and adolescents with direct measurements of radioactivity in the thyroid (so-called direct thyroid measurements) performed in May-June of 1986; (2) at the second level, group doses by year of age and by gender were estimated for the population of 748 localities (with 208,400 children aged 1-18 in 1986) where direct thyroid measurements of good quality were performed on some of the residents; and (3) at the third level, group doses by age and by gender were estimated for the population of the localities where no thyroid measurements were made in 1986. The third-level doses were then aggregated over the population of each oblast. Data, models and procedures required for each level of thyroid dose estimation are described in the paper. At the first level, individual doses were found to range up to 27,000 mGy, with geometric and arithmetic means of 100 and 300 mGy, respectively. At the second level, group doses were found to be highest for the younger children (aged 1 to 4 years); doses for the older children (aged 16 to 18 years) were 3.5 times smaller. At the third level, average population-weighted doses were found to exceed 35 mGy in the five northern oblasts closer to the Chornobyl reactor site; to be in the 14- to 34-mGy range in seven other oblasts, Kyiv city and Crimea; and to be less than 13 mGy in all other oblasts.     

A cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: objectives, design and methods

The thyroid gland in children is one of the organs that is most sensitive to external exposure to X and gamma rays. However, data on the risk of thyroid cancer in children after exposure to radioactive iodines are sparse. The Chornobyl accident in Ukraine in 1986 led to the exposure of large populations to radioactive iodines, particularly (131)I. This paper describes an ongoing cohort study being conducted in Belarus and Ukraine that includes 25,161 subjects under the age of 18 years in 1986 who are being screened for thyroid diseases every 2 years. Individual thyroid doses are being estimated for all study subjects based on measurement of the radioactivity of the thyroid gland made in 1986 together with a radioecological model and interview data. Approximately 100 histologically confirmed thyroid cancers were detected as a consequence of the first round of screening. The data will enable fitting appropriate dose-response models, which are important in both radiation epidemiology and public health for prediction of risks from exposure to radioactive iodines from medical sources and any future nuclear accidents. Plans are to continue to follow-up the cohort for at least three screening cycles, which will lead to more precise estimates of risk.     

Trends in infant leukaemia in West Germany in relation to in utero exposure due to the Chernobyl accident

A temporary increase in the incidence of infant leukaemia in Greece was reported by Petridou et al., which was attributed to in utero exposure to ionising radiation resulting from the Chernobyl accident. We performed a similar analysis based on the data of the German Childhood Cancer Registry in order to check whether the observation could be confirmed by means of independent data. Applying the same definitions as Petridou et al., we also observed an increased incidence of infant leukaemia in a cohort of children born after the Chernobyl accident. More detailed analyses, regarding areas with different contamination levels and dose rate gradients over time after the accident, showed, however, no clear trend with regard to exposure. It would therefore appear less likely that the observed effect was caused by exposure to ionising radiation due to the Chernobyl accident. Received: 30 January 1998 / Accepted in revised form: 23 April 1998     

Thyroid cancer incidence in the Ukraine after the Chernobyl accident: comparison with spontaneous incidences

The thyroid cancer incidence in the Ukraine among those born in the period 1968–1986 was analyzed with the aim to identify the enhancement due to the Chernobyl accident. Since any Ukrainian data referring to the time period before the accident are scarce and the variation of spontaneous incidences in other countries is immense, the Ukrainian incidences in the period 1986–1989 were used to estimate the baseline risk. Following 1990, the incidence in the southern part of the Ukraine increased by about 30%, independent of age. In the other parts the increase of the incidence depended on age at exposure. In the age group of 9-year-old children, the incidences in three regions defined as the `high-dose area', the northern, and the middle oblasts, increased by factors of 50, 20, and 6, respectively. These rates (1991–1995) are well above spontaneous rates in other countries. In the age group of 17-year-old juveniles, the incidence increased by a factor of 6 for the `high dose area' and in the three northern oblasts, whereas in the nine `middle' oblasts it was similar to the incidence of the `southern' Ukraine. These rates are within the range found in other countries.     

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.     

Thyroid cancer risk in Belarus after the Chernobyl accident: Comparison with external exposures

Within the time period 1990–1993, childhood thyroid cancer incidence due to the Chernobyl accident increased dramatically in Belarus, especially with regard to the birth cohort January 1, 1971, to May 31, 1986. This rise subsequently slowed down, i.e. during the period 1994–1996. The respective data were analysed and compared with the results of an analysis on the time dependence of thyroid cancer incidence in a pooled cohort of persons who had been exposed during childhood to external radiation with high dose rates. Concerning the period of 5–10 years following exposure, the excess absolute cancer risk per unit thyroid dose in the latter (external) exposure group was found to exceed the one in the Belarus group by a factor of two. This difference, however, is not statistically significant. The age-adjusted average excess absolute risk per unit thyroid dose for the period of 5–50 years following external childhood exposure was found to be 8 female and 14 male cases per 10⁴ person-year · Gy, which is a factor about 2.5 times higher than for the non-adjusted risk in the pooled cohort, as reported by Ron et al. in 1995. Assessments of future excess thyroid cancer cases due to the Chernobyl accident were done on the basis of the time dependence of thyroid cancer risk following external exposure. The thyroid cancer incidence among the birth cohort considered in Belarus and for a period starting from the cessation of the available observation data (1 January 1997) and extending to 50 years after the Chernobyl accident has been estimated to be about 15,000 cases, with an uncertainty range of 5000–45,000 cases. According to our calculations, 80% of these cases exceed the baseline risk under enhanced thyroid surveillance. Received: 8 June 1999 / Accepted in revised form: 20 November 1999     

15 years after the accident at the Chernobyl Nuclear Power Plant

Health effects as a result of the accident at the Chernobyl nuclear power plant occurred in 1986 are considered in the paper. Wrong prognosis of the health effects with respect to mortality and morbidity among the population exposed to low radiation doses is shown. Proven increase in thyroid cancer cases among people who were children aged from 0 to 18 at the time of the accident is shown. Linear relationship between thyroid cancer cases and dose to thyroid ranged from 0.2 to 4.0 Gy is considered. An additional absolute risk of thyroid cancer in children varies in the range 1.9-2.6 cases per 10(4) person-year Gy. During the fifteen years following the accident no cases of acute and chronic radiation sickness have been revealed because the population living in contaminated areas received low radiation doses. Also, exposures to low radiation doses did not result in excess of malignant tumors among population. In some cases the outcomes of acute radiation sickness were as follows: radiation damages to the skin, cancer cataracts, development of oncopathology.     

Thyroid cancer incidence among liquidators of the Chernobyl accident

The increase of thyroid cancer incidence rate among children living in the Chernobyl contaminated territories of Belarus, Russia and Ukraine has widely been accepted. Our current work deals with thyroid cancer incidence in the cohort of liquidators (99024 persons) living in 6 regions of Russia: North-West, Volgo-Vyatsky, Central-Chernozemny, Povolzhsky, North-Caucasus and Urals. In the period 1986-1998, a total of 58 thyroid cancer cases were detected in this cohort. We found a statistically significant increase of the thyroid cancer incidence rate in liquidators as compared to the baseline (male population of Russia) level (SIR=4.33, 95% CI: 3.29; 5.60). It was demonstrated that there is no dependence of incidence rates due to external radiation exposure (ERR/Gy=-2.23, 95% CI: -4.67; 0.22).     

Post-Chernobyl thyroid cancers in Ukraine. Report 2: risk analysis

On April 26, 1986, the worst nuclear reactor accident to date occurred at the Chornobyl (Chernobyl) power plant in Ukraine. Millions of people in Ukraine, Belarus and Russia were exposed to radioactive nuclides, especially (131)I. Since then, research has been conducted on various subgroups of the exposed population, and it has been demonstrated that the large increase in thyroid cancer is related to the (131)I exposure. However, because of study limitations, quantified risk estimates are limited, and there remains a need for additional information. We conducted an ecological study to investigate the relationship between (131)I thyroid dose and the diagnosis of thyroid cancer in three highly contaminated oblasts in Northern Ukraine. The study population is comprised of 301,907 persons who were between the ages of 1 and 18 at the time of the Chornobyl accident and were living in 1,293 rural settlements in the three study oblasts. Twenty-four percent of the study population had individual thyroid dose estimates and the other 76% had "individualized" estimates of thyroid dose based on direct thyroid measurements taken from a person of the same age and gender living in the same or nearby settlement. Cases include 232 thyroid cancers diagnosed from January 1990 through December 2001, and all were confirmed histologically. Dose-response analyses took into account differences in the rate of ultrasound examinations conducted in the three study oblasts. The estimated excess relative risk per gray was 8.0 (95% CI = 4.6-15) and the excess absolute risk per 10,000 person-year gray was estimated to be 1.5 (95% CI = 1.2-1.9). In broad terms, these estimates are compatible with results of other studies from the contaminated areas, as well as studies of external radiation exposure.     

Centrosome amplification as a possible mechanism for numerical chromosome aberrations in cerebral primitive neuroectodermal tumors with TP53 mutations

Although alterations in chromosome number have frequently been detected in human tumor cells and associated with tumor initiation and progression, the causal mechanisms are still not understood. One protein known to be involved in maintaining genetic stability is tumor suppressor p53. In mice, p53 has been implicated in the maintenance of diploidy (Cross et al., 1995) and the regulation of centrosome duplication (Fukasawa et al., 1996). Here we report on cerebral primitive neuroectodermal tumors that lacked the wild-type p53 gene (TP53) and showed multiple numerical chromosome aberrations, as detected by comparative genomic hybridization. In these tumors, the centrosome number was significantly higher than in a control tumor without a detected TP53 mutation and with few chromosomal imbalances. These findings indicate that abnormal centrosome amplification can occur in human tumors lacking wild-type TP53 and may be a mechanism by which numerical chromosome aberrations are generated.     

Thyroid cancer incidence in Ukraine: trends with reference to the Chernobyl accident

For the first time, a comparative analysis of thyroid cancer incidence in Ukraine after the Chernobyl accident was done in a cohort that is almost as large as the general population. On the basis of thyroid doses from radioactive iodine in individuals aged 1-18 years at the time of accident, geographic regions of Ukraine with low and high average accumulated thyroid doses were established and designated "low-exposure" and "high-exposure" territories, respectively. A significant difference of thyroid cancer incidence rates as a function of time between the two territories was found. That is, the increase in the incidence was higher in high-exposure regions than in low-exposure regions. The incidence rates varied substantially among the different attained age-groups, especially in the youngest one (up to 19 years old). The analysis that was adjusted for screening and technological effects also indicated that in the high-exposure regions, thyroid cancer incidence rates at the age of diagnosis of 5-9, 10-14 and 15-19 years were significantly higher in those born in 1982-1986 compared to those born in 1987-1991, while in the low-exposure regions, no significant difference was observed. The observed probable excess of radiation-induced thyroid cancer cases in adults exposed to radioactive iodine from the Chernobyl accident, especially in females, may be due to the high power of the present study. However, it should be noted that our investigation was not essentially free from ecological biases.     

Localization of the rat immunoglobulin lambda light chain locus to chromosome 11

Previous experiments using rat/mouse somatic cell hybrids have localized the rat c-myc gene to chromosome 7 (Sümegi et al. 1983), the rat immunoglobulin kappa locus to chromosome 4 (Perlmann et al. 1985), and the rat immunoglobulin heavy chain locus to chromosome 6 (Pear et al. 1986). Using a similar approach, we now report the localization of the rat immunoglobulin lambda light chain locus to chromosome 11.     

Chromosomal localization of GPR48, a novel glycoprotein hormone receptor like GPCR, in human and mouse with radiation hybrid and interspecific backcross mapping

We report the chromosomal localization in both mouse and human of a novel G-protein-coupled receptor, GPR48, which resembles glycoprotein hormone receptors, that may be implicated in Wilms tumor deletion syndromes such as WAGR. This receptor forms a novel sub-family of glycoprotein hormone-like GPCRs. We have mapped this receptor to human chromosome 11p14-->p13 by several approaches, including radiation hybrid and interspecific backcross mapping, and show that GPR48 is close to BDNF. This data differs from the recently published mapping of LGR4 (5q34-->q35.1) (Hsu et al., 1998). Additionally, we show that Gpr48 and Bdnf are tightly linked on mouse chromosome 2, in a region with conserved synteny to human 11p14-->p13.     

Results of a cytogenetic study of children from radionuclide-contaminated goiter endemic zone of the Rivno region of Ukraine

Under the conventional cytogenetical examination of 6 different children groups (with and without non-stohastic thyroid pathology, exposed and nonexposed to the iodine isotopes in 1986) from the goiter endemic zone of Ukraine which belongs to the territory contaminated by 137Cs radionuclides, the identical to the spontaneous level of somatic chromosome mutagenesis of the last decade in all observed groups with the tendency to increasing of stable aberrations in some persons had been established.     

A High-Resolution Interval Map of the q21 Region of the Human X Chromosome

In a previous study, we have developed a panel of chromosomal rearrangements for the physical mapping of the q13-q21 region of the human X chromosome (Philippe et al., Genomics 17: 147-152, 1993). Here, we report the physical localization of 36 additional polymorphic markers by polymerase chain reaction analysis. The high density of chromosomal breakpoints in Xq21 allows us to map 58 DNA loci in 22 intervals. As a result, this segment of the X chromosome is saturated with approximately three sequence tagged sites per megabase of DNA, which will facilitate the construction of a YAC contig of this region.     

Major Factors Affecting Incidence of Childhood Thyroid Cancer in Belarus after the Chernobyl Accident: Do Nitrates in Drinking Water Play a Role?

One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (¹³¹I) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the ¹³¹I-related risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiation-related risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer.