A Systematic Review of Thyroid Cancer After the Chernobyl Accident

ABSTRACT

Background: Following the immediate fallout of the Chernobyl nuclear accident, many epidemiologic studies were conducted to ascertain the effects of ionizing radiation on cancer incidence and prevalence. The aim of this study was to understand the long-standing trends that can be attributed to the disaster through extended epidemiologic studies that assess thyroid cancer within highly irradiated populations.

Methods: The analyses within this review encompass a variety of study designs and methodology with incidence being assessed through risk projection models and international cancer registries. Given the complexity of this incident, the analysis has been supplemented by appropriate case-control and cohort data to further understand the dose-response and radiobiological relationships between ionizing radiation and cancer.

Results: The risk projection models indicate that Chernobyl may have been responsible for up to 16,000 cases of thyroid cancer due to exposure to ¹³¹I and 1,000 thyroid cancer deaths. Additionally, some of the countries within the most highly contaminated countries show markedly higher thyroid cancer incidence rates than their more western counterparts.

Conclusions: A review of the Chernobyl disaster indicates that the event is responsible for a noticeably increased incidence rate of thyroid cancer within highly contaminated areas due to the high ¹³¹I thyroid dosages.

INTRODUCTION

On April 26, 1986, the Chernobyl power plant in Ukraine suffered a catastrophic reactor accident that shocked the world in its severity and scope. Massive amounts of radioactive material were jettisoned thousands of meters into the atmosphere, resulting in the release of several types of radionuclides, consisting of (1.2-18) x 10¹⁸ Bq of short-lived ¹³¹I and roughly 1.4 x 10¹⁷ Bq of long lived ¹³⁴Cs and ¹³⁷Cs.¹ Nuclear fallout quickly contaminated the surrounding communities and dispersed these harmful radionuclides across Europe. Dispersion was concentrated within Belarus, Ukraine, and what is today the western part of the Russian Federation, here, ingestion of food stuffs irradiated with radioactive iodine resulted in those populations (particularly children) receiving significant doses to the thyroid gland.² To this day, the area surrounding the facility is closed to the general public in an “exclusion zone” that encompasses some 30 square kilometers around the site. While many of the results of the disaster were clearly obvious to the public through horrific scenes of radiation poisoning and an irradiated habitat, the more insidious effects of radiation exposure have manifested themselves in increased cancer burden both within the immediate population as well as the greater population of Europe.

While much study has gone into the assessment and containment of the disaster, epidemiological pursuits have focused on the 3 most contaminated countries and confirmed a causal link between the observed risk of thyroid cancer and exposure to the radioactive isotope ¹³¹I from the Chernobyl fallout amongst those who were adolescents or children when the accident occurred.^3-5 Other cancers, including leukemia, have been researched, but these studies have not been able to clearly demonstrate an association with radiation exposure. Additionally, there have been more recent studies that suggest a possible small increase in the incidence of premenopausal breast cancer in the most contaminated districts found within Belarus, the Russian Federation, and Ukraine.⁸ However, these findings and studies need further validation through more robust epidemiologic studies that include amongst other measures, careful individual dose reproduction in accordance with dose and exposure models.

The primary objective of this study is to assess and evaluate the burden of thyroid cancer incidence within the countries most impacted by the Chernobyl accident, as well Europe as a whole.

MATERIALS AND METHODS

There are a variety of approaches to understand and estimate the thyroid cancer burden in Europe due to the Chernobyl accident. This review utilizes multiple means of analysis, including: radiation dose reconstruction, risk projection models and studying updated incidence rates.

Data Sources

Incidence and mortality data were obtained through the International Agency for Research on Cancer (IARC) and further derived from the Global Cancer Observatory (GLOBOCAN). Information that was found within contributing sources and references was drawn from the United Nations Economic Commission for Europe (UNECE), United States Census Bureau, the Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), as well as other international databases and organizations.

Study Population and Cases

Analyses ranged in their scope and manner of quantification, with predictive risk models and ecological studies providing the majority of data. The distribution of thyroid cancer and radiation dosage were analyzed by age group, dose received, year of diagnosis, and country. Within European countries, there were two distinct groups that constituted the basis for establishing the severity of irradiated iodine, those three countries most contaminated by the disaster and the rest of Europe. Predictive risk modeling included analysis that focused on 40 countries. Due to available cancer time-trend data, incidence was limited to 9 countries with 3 of those countries containing multiple cancer registries. Except in more recent incidence data, populations were aggregated together to assess the overall cancer burden that effects the two main areas of interest.

Radiation Dosage

Dosage reconstruction for European countries was found through country-specific radiation monitoring databases and their subsequent estimates of exposure levels on individual populations. For Belarus, Ukraine, and the Russian Federation, detailed information was obtained through publications by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) and the UN Chernobyl Forum Report.^1,7 As detailed within Cardis,² data on ¹³⁷Cs deposition density and activity of ¹³¹I and ¹³⁷Cs foodstuffs during the first year following the disaster were used to estimate the country and region specific estimates of whole-body contamination of the thyroid due to ¹³¹I. Imprecise dosage values were considered the lowest in Belarus, Ukraine, and the Russian Federation, which have extensive and robust radiation monitoring systems in place.

Projection Risk Models

Projection risk models used within this summary analysis were based the risk models constructed by the US National Research Council’s Committee on the Biological Effects of Ionizing Radiation (BEIR VII).⁶ These models combine excess relative risk (ERR) and excess absolute risk (EAR) models, both of these risk measures were written as a linear function of dose, contingent on sex, age at exposure and attained age. The BEIR VII risk models for thyroid cancer were based upon published combined analyses of the data on atomic bomb survivors and medically exposed cohorts.⁹ Projection risk estimates relating to radiation exposure over time assumed that population demographics and cancer incidence would remain constant from 1986 to 2065. As presented in the BEIR VII, the risk estimates summarized within this review, the risk estimates are accompanied by substantial and subjective uncertainty intervals that quantify uncertainty sources: (1) sampling variability in risk model estimates from atomic bomb survivor data, (2) uncertainty in the correct value of dose and dose-rate effectiveness factor (DDREF), and (3) all solid cancers and leukemia, uncertainty in using Japanese atomic bomb survivors to estimate risks in populations with dissimilar baseline risks.⁶

Trends in Thyroid Cancer Incidence

Incidence data were assessed through an ecological survey of readily available cancer registries produced by IARC and its subsequent publications GLOBOCAN and CI5.¹⁰ Due to certain country-specific thyroid cancer rates being unavailable, Belarus was used as a proxy for high contamination dosage when compared to lower does found throughout Europe. Graphs, tables, and figures were compared by country-specific cancer, based upon sex, age group (when available), and time. Subsequent data were compared to radiation dosage maps and registries. Based upon these input factors, thyroid cancer attributed to radiation from the Chernobyl accident was assessed for an approximate lag time of approximately 5 years and onwards. Additionally, as found within the Cardis analysis,² the effect of dosage and thyroid cancer incidence was examined using Poisson regression to create a registry organization scheme that could be subdivided into various dosage groups.

RESULTS

Radiation Doses Attributed to Chernobyl

Figure 1.²

Following the accident in 1986, radiation doses were highest in Belarus and Ukraine, with the average cumulative whole-body dose exceeding 0.5 mSv. At a 2005 follow-up measurement, the average cumulative country-specific whole-body doses were respectively, 2.8 mSv in Belarus, 5.1 mSv in heavily contaminated areas of the Russian Federation and 2.1 mSv in Ukraine.² The average cumulative dose through 2005 for highly irradiated areas in Belarus and Russian Federation was estimated to be roughly 20 times higher (approximately 10 mSv) when compared to Europe (0.5 mSv) as a whole. As seen in Figure X,² the spatial distribution of dosage to the thyroid gland from ¹³¹I is shown for children younger than 5 years old and for adults at least 30 years old in 1986. Doses of ¹³¹I were markedly higher than whole-body doses due to external and internal exposure to longer-living radionuclides. Amongst these higher thyroid doses, the highest average dosages were received in the Gomel region of Belarus, in the Bryansk region of the Russian Federation and in the Zhytomir Region of Ukraine.^2,7

Risk Projections

Table 1.²

Predicted thyroid cancer cases and deaths between 1986 and 2065 (with the latter indicating values 80 years following the accident) are shown in Table 1. Country groups were determined upon average thyroid dose with the lowest group receiving <5 mSv and the highest group receiving ≥100 mSv. For thyroid cancer, the estimated attributable fractions (AFs) range for countries contaminated with ¹³¹I, with the least contaminated ranging from 0.08%, to 12% in the most contaminated countries (average thyroid dose <5 mSv and an average thyroid of at least 100 mSv). Uncertainty intervals for the estimates are particularly wide, ranging from 3,400 to 72,000 additional thyroid cancer cases by 2065. Roughly half of the possible additional cases are expected to occur in areas with average dosages of at least 25 mSv, representing only 3% of the population under study. Amongst the massive number of predicted radiation-induced cases of thyroid cancer, 90% are expected to occur in those younger than 15 years of age when the Chernobyl accident transpired.

Cancer Incidence Trends

Figure 2.¹¹      Figure 3.¹²

Incidence rates for thyroid cancer incidence across Europe are found within Figures 11 and 12. Figure 11 shows the female, Thyroid Age Standardized Incidence Rate amongst various European countries. Figure 12 shows the male, Thyroid Age Standardized Incidence Rate amongst various European countries. Data measurements fall within the age period of 1953 and 2012, with the majority of countries first reporting data in 1983. Although increasing trends can be observed amongst both genders and all countries, Belarus shows one of the most drastic increases with an overall incidence (0.49 to 3.25 for males, 1.72 to 14.78 for females). As seen in the comparison of the two groups, females show an approximate 4.5 times increase in thyroid cancer incidence compared to males.

Figure 4.²

Figure 4 shows the trends of thyroid cancer by age at diagnosis and registry grouped by thyroid dose. Trends indicate that incidence increases in the 3 groups with the highest dose. The effects of geographic distribution can also be seen within the incidence of thyroid cancer as those European countries further west show decreased incidence in conjunction to decreased thyroid doses. The increase was greatest among children exposed age <15 and was most pronounced in the registries showing the highest dose. Analysis performed on all registries from 1981 to 2002 indicate statistically significant associations (p<0.05) between the average dose in each registry and the incidence of all cancers.² Further analyses of the linear contrasts between registries and groups indicated that although cancer incidence had been increasing in Europe since 1981, the slope actually decreased after 1991 for all cancers. Since 1991, only thyroid cancer has shown a consistent, statistical increase in the slope for cancer incidence.

DISCUSSION

Conclusions

This systematic review serves as an updated assessment for the burden and severity of thyroid cancer incidence as a result of increased ionizing radiation attributed to ¹³¹I from the Chernobyl accident. The strength behind this analysis includes the assessment and synthesis of both old and updated data on radiation exposures, resulting in an evaluation of the unique pathology and spatial distribution of iodine-related radionuclides in Europe. The analysis includes predictions for the number of thyroid cancer cases due to radiation from the Chernobyl accident to the year 2065 using projected risk models based upon previous instances of populations exposed to radiation.⁷ Due to the susceptibility of children to high 131I thyroid doses, the radiation received has been proven through various epidemiological studies to have a demonstrated association between radiation dosage to the thyroid and thyroid cancer in the general population.^13,14

Limitations

As the primary intent of this review was to understand the general trends of thyroid cancer incidence in Europe and highly contaminated areas, more complex factors such as pathology and dosimetry were only briefly covered. Because the spread of radionuclides was relatively limited outside of Belarus, the Russian Federation and Ukraine, epidemiological studies have had very little power to ascertain an association between the Chernobyl accident and cancer risk. Given the resource intensive nature of the surveillance required to fully assess the cancer burden associated with low-level radiation exposure, there have not been systematic studies by international organizations within the past 15 years to ascertain the changes in cancer incidence more broadly. With the latency period being approximately 20 years for most of the cancers associated with radiation exposure, only now are the full effects of the Chernobyl accident beginning to manifest themselves.

Recommendations

Further analyses to better understand the overall cancer burden found within Europe as a result of the Chernobyl accident could explore cancers that are only now falling within the relatively long latency period seen between exposure and occurrence for the many categories of radiation-related cancers. Future studies might investigate the possible influences of other factors, such as screening bias, socioeconomic factors, as well as controlling for iodine deficiencies found throughout the most heavily irradiated areas.  Careful analytical studies that follow-up with the most exposed populations on specific outcomes, such as breast cancer incidence, will aid in updating future risk prediction models that will be used to evaluate the true burden of cancer from the Chernobyl disaster.

REFERENCES

1. United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). Sources and effects of ionizing radiation- Volume II, Effects. New York: United Nations, 2000.
2. Cardis, Elisabeth, Daniel Krewski, Mathieu Boniol, Vladimir Drozdovitch, Sarah C. Darby, Ethel S. Gilbert, Suminori Akiba, et al. “Estimates of the Cancer Burden in Europe from Radioactive Fallout from the Chernobyl Accident.” International Journal of Cancer 119, no. 6 (2006): 1224–1235. https://doi.org/10.1002/ijc.22037.
3. Cardis E, Kesminiene A, Ivanov V, Malakhova I, Shibata Y, Khrouch V, Drozdovitch V, Maceika E, Zvonova I, Vlassov O, Bouville A, Goulko G, et al. Risk of thyroid cancer after exposure to 131I in childhood. J Natl Cancer Inst 2005;97:724-32.
4. Davis S, Stepanenko v, Rivkind N, Kopecky KJ, Voilleque P, Shakhtarin V, Parshkov E, Kulikov S, Lushnikov E, Abrosimov A, Troshin V, Romanova G, et al. Risk of thyroid cancer in the Bryansk oblast of the Russian Federation after the Chernobyl power station accident. Radiat Res 2004; 162: 241-8.
5. Jacob P, Bogdanova TI, Buglova E, Cherpurniy M, Demidchik Y, Gavrilin Y, Kenigsberg J, Meckbatch R, Schotola C, Shinkarev S, Tronko MD, Ulanovsky A, et al. Thyroid cancer risk in areas of Ukraine and Belarus affected by the Chernobyl accident. Radiat Res 2006;165:1-8.
6. US National Research Council. Health risks from exposure to low levels of ionizing radiation. BEIR, VII Report, phase II. Washington, DC: National Academy of Science, 2005.
7. United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). Sources and Effects of Ionizing Radiation. New York: United Nations, 2008.
8. Pukkala E, Kesminiene A, Polyakov S, Ryzhov A, Drozdovitich V, Kovgan LN, Kyyronen P, Malakhova I, Gulak L, Cardis E. Breast Cancer in Belarus and Ukraine after the Chernobyl accident. Int J Cancer 2006; www3.interscience.wiley.com, doi: 10.1002/ijc.21885
9. Ron E, Lubin JH, Shore RE, Mabuchi K, Modan B, Pottern LM, Schneider AB, Tucker MA, Boice JD, Jr. Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. Radiat Res 1995;141:259-77
10. International Agency for Research on Cancer (IARC). CI5plus. 2019 https://gco.iarc.fr/
11. International Agency for Research on Cancer (IARC). CI5plus. 2019. http://ci5.iarc.fr/CI5plus/old/Graph4p.asp?cancer%5B%5D=250&female=2&country%5B%5D=11200000&country%5B%5D=20300000&country%5B%5D=20800000&country%5B%5D=23300000&country%5B%5D=25000000&country%5B%5D=27600000&country%5B%5D=61600700&country%5B%5D=75600000&country%5B%5D=82605000&sYear=1950&eYear=2012&stat=3&age_from=1&age_to=18&orientation=1&window=1&grid=1&line=2&moving=1&scale=0&submit=%C2%A0%C2%A0%C2%A0Execute%C2%A0%C2%A0%C2%A0
12. International Agency for Research on Cancer (IARC). CI5plus. 2019. http://ci5.iarc.fr/CI5plus/old/Graph4p.asp?cancer%5B%5D=250&male=1&country%5B%5D=11200000&country%5B%5D=20300000&country%5B%5D=20800000&country%5B%5D=23300000&country%5B%5D=25000000&country%5B%5D=27600000&country%5B%5D=61600700&country%5B%5D=75600000&country%5B%5D=82605000&sYear=1950&eYear=2012&stat=3&age_from=1&age_to=18&orientation=1&window=1&grid=1&line=2&moving=1&scale=0&submit=%C2%A0%C2%A0%C2%A0Execute%C2%A0%C2%A0%C2%A0
13. UN Chernobyl Forum Expert Group Health (EGH). Health effects of the Chernobyl accident and special health care programmes. Geneva, Switzerland: World Health Organization, 2006.
14. Cardis E, Howe G, Ron E, Bebeshko VG, Bogdanova T, Bouville A, Carr Z, Chumak V, Davis S, Demidchik Y, Drozdovitch V, Gentmer N, et al. Cancer consequences of the Chernobyl accident: 20 years after. J Radiol Prot 2006;26:(doi:10.1088/0952-4746/26/2/001).