
==== Front
Ecotoxicol Environ Saf
Ecotoxicol Environ Saf
Ecotoxicology and Environmental Safety
0147-6513
1090-2414
Elsevier

S0147-6513(24)00865-0
10.1016/j.ecoenv.2024.116789
116789
Article
Recent insights into trends of thyroid cancer incidence in Lithuanian population exposed to Chernobyl fallout early in life
Steponaviciene Rita rita.steponaviciene@nvi.lt
a⁎
Maceika Evaldas b
Kesminiene Ausrele c
Smailyte Giedre giedre.smailyte@nvi.lt
de⁎⁎
a External Beam Radiotherapy Department, National Cancer Institute, Santariskiu Str. 1, Vilnius LT-08406, Lithuania
b State Research Institute Center for Physical Sciences and Technology, Savanorių Ave. 231, Vilnius 02300, Lithuania
c Environment and Lifestyle Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), 25 avenue Tony Garnier, CS 90627, Lyon Cedex 07 69366, France
d Public Health Department, Institute of Health Sciences, Faculty of Medicine, Vilnius University, M.K. Ciurlionio. 21, Vilnius LT-03101, Lithuania
e Laboratory of Cancer Epidemiology, National Cancer Institute, P. Baublio 3B, Vilnius LT-08406, Lithuania
⁎ Corresponding author. rita.steponaviciene@nvi.lt
⁎⁎ Corresponding author at: Laboratory of Cancer Epidemiology, National Cancer Institute, P. Baublio 3B, Vilnius LT-08406, Lithuania. giedre.smailyte@nvi.lt
15 9 2024
15 9 2024
283 11678930 4 2024
20 7 2024
24 7 2024
© 2024 Published by Elsevier Inc.
2024

https://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
In the last three decades, an increase in thyroid cancer incidence has been observed worldwide, as well as in Lithuania. Although the rise was linked to overdiagnosis, the role of lifestyle and environmental factors, including exposure to ionizing radiation, cannot be excluded. In our retrospective study, we aimed to assess the association between the average age-specific thyroid dose due to the radioactive iodine uptake during childhood and adolescence from the Chernobyl fallout in Lithuania, and the trends of incidence of thyroid cancer from 1991 to 2015 in different regions. Averaged age-dependent thyroid doses were estimated for every municipality based on radioiodine activity in milk, reconstructed from available 131I activity measurements in the grass. Thyroid cancer incidence rates were calculated for the entire population and for two age at the time of exposure groups: 0–19 years and 0–9 years. Thyroid cancer relative risk (RR) was estimated for three municipality-specific thyroid dose (for 0-year-old babies) categories: less than 100 mGy (reference group), 100–199 mGy, and ≥200 mGy. Over the study period (1991–2015), a total of 5664 cases of thyroid cancer were registered in the entire Lithuanian population; 817 cases in the age group from 0 to 19 years at the time of the Chernobyl accident, and 266 cases in the age group from 0 to 9 years. Age-standardized thyroid cancer incidence rates have notably increased since 2000, peaked in 2009 (especially in females), and then slightly decreased and stabilized. The estimated average municipality-specific age-dependent thyroid doses ranged from 270 mGy in western Lithuania to 1.5 mGy in central and northern Lithuania. For the age group of 0–19 years at the time of the accident, in the period 1991–1995, the thyroid cancer relative risk was significantly increased (RR 3.91; 95 % CI: 1.27–10.29, p=0.01) in the highest dose category, compared to the lowest (although based on a small number of cases). For the age group 0–9 years at the time of the accident, a tendency of increased RR in the highest dose category appeared in the most recent period, 2011–2015. Our observations need to be confirmed by further following trends of thyroid cancer incidence in the cohort of 0–19-year-old Lithuanians at the time of the Chernobyl accident.

Highlights

• The Chernobyl disaster had a long-term health impact on those exposed to radiation early in life.

• The effects of this accident were far-reaching and continue to be studied to this day.

• Reconstructed dose of 131I to the thyroid showed a wide range variation among Lithuania’s regions.

• In areas with doses over 200 mGy in early life, thyroid cancer rates increased for both sexes.

Keywords

Chernobyl accident
Thyroid cancer incidence
Ionizing radiation
Dosimetry
Children, adolescents
Lithuania
Edited by Dr G Liu
==== Body
pmc1 Introduction

In the last three decades, a worldwide increase in thyroid cancer incidence has been observed (Greenlee et al., 2001, Kitahara and Sosa, 2016, Li et al., 2020, Vaccarella et al., 2016). Several authors tried to explain that the main reasons are increased surveillance and improved diagnostic tools (Howlader et al., 2019, Li et al., 2020; Steliarova-Foucher et al., 2017). Nevertheless, this type of cancer remains rare among children and adolescents – in the USA and Europe, it accounts for 1.5–3 % of all cancers in this age group (Howlader et al., 2019, Li et al., 2020).

Lithuania is no exception to this, according to the analysis of the thyroid cancer incidence trends in 1978–2003 (Smailyte et al., 2006) or more recently (Miranda-Filho et al., 2021). Although the rise in thyroid cancer incidence accelerated in the period between 2000 and 2003, most likely due to the more frequent application of ultrasound-guided fine needle aspiration biopsy (Vaccarella et al., 2016), it stabilized around 2009 (Miranda-Filho et al., 2021).

However, it has been argued that overdiagnosis alone does not fully explain the observed increases (Smittenaar et al., 2016) and might be accompanied by exposure to other factors, such as stable iodine intake, medical radiation, and increased obesity prevalence (Caini et al., 2015, Cao et al., 2017, Suzuki et al., 2008). Therefore, the role of other potential risk factors of thyroid cancer that possibly contributed to the observed epidemics of thyroid cancer, particularly papillary thyroid cancer, should be explored.

Exposure to ionizing radiation, including radioactive iodine, is among the best-established factors that may cause thyroid cancer, mainly if exposure occurs early in life (IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2000; UNSCEAR, 2022). The dramatic increase in thyroid cancer incidence in Belarus, four regions of Russia, and Ukraine, among those who were children and adolescents at the time of the Chernobyl accident, has been linked to exposure to radioactive iodines from the Chernobyl fallout (UNSCEAR, 2022). Factors such as iodine deficiency, non-cancerous thyroid findings, family history of thyroid cancer, and elevated body mass index may have further escalated the risk of thyroid cancer in children affected by the nuclear accident (Shakhtarin et al., 2003, Cardis et al., 2005, Jacob et al., 2006, Zupunski et al., 2019).

Studies conducted in European countries outside Belarus, Russia and Ukraine, particularly in Scandinavia, investigated the impact of radioactive fallout from the Chernobyl accident on the risk of thyroid cancer among children and adolescents and found no association (Sali et al., 1996, But et al., 2006).

Due to the meteorological situation in the first days after the accident, the radioactive iodines were also deposited over the territory of Lithuania (UNSCEAR, 2011). According to Cardis et al. (2006), the estimated average thyroid dose from Chernobyl fallout in the whole territory of Lithuania was between 10 and 25 mSv, similar to Minsk and western Grodno regions of Belarus. It was predicted that in 2065 in Lithuania, the fraction of thyroid cancer cases attributable to exposure to 131I before the age of 15 years should reach up to 2.14 % (Cardis et al., 2006).

Although the average estimated dose in Lithuania was relatively low (Cardis et al., 2006), the measurements of cow's milk and pasture grass in Lithuania's Southern and Western regions in May 1986 showed relatively high 131I activity of >3700 Bq/L and >30 kBq/kg in milk and grass, correspondingly (Nedveckaite and Filistovic, 1995; Nedveckaite et al., 2004). We, therefore, aimed to evaluate the association between exposure to radioactive iodine within the first weeks after the Chernobyl accident and the incidence of thyroid cancer in Lithuania from 1991 to 2015.

The specific aims of this study were: to estimate the age-specific thyroid doses in all municipalities of Lithuania; and to assess their impact on the thyroid cancer risk among those who were children and adolescents (age 0–19 years) at the time of the Chernobyl accident.

2 Material and methods

2.1 Cancer incidence and population data

We conducted a retrospective study encompassing the period from 1986 to 2015. Follow-up for thyroid cancer incidence started in 1991 to allow for a 5-year latency period for possibly radiation-related thyroid cancer to occur. Data on thyroid cancer incidence were obtained from the Lithuanian Cancer Registry (Registry). The Registry covers the entire population of the Republic of Lithuania (3.04 million according to the 2011 census). It is located at the National Cancer Center, which has recently operated as the National Cancer Institute. The main data sources are notifications collected from all hospitals and diagnostic centers in Lithuania. This information was complemented by death certificates stating cancer diagnosis and by notifications from regional health centers. The study was based on all cases of thyroid cancer reported to the Registry during 1991–2015.

We used the 1986–2015 population data (by age, sex, and calendar year) of the Department of Statistics of the Republic of Lithuania. For comparability and integrity of the data, we chose to follow the administrative division system of Lithuania that was in place in 1989 (44 districts and 11 cities). However, a partial administrative reform took place in 1994.

Thyroid cancer incidence rates were calculated for the entire population and for two age at the time of exposure groups. The first group included those who were 0–9 years old at the time of the Chernobyl accident, whereas the second group (aged 0–19 years) also included those who were adolescents and young adults. Incidence rates were tabulated by municipalities and 5-year period of diagnosis.

2.2 Dosimetry

At the time of the Chernobyl accident, the surface winds blew from the southeast. The initial explosions and heat carried volatile radioactive materials into the upper atmosphere, where they were then carried by the jet stream over the Western part of Belarus, and the Southern and Western areas of Lithuania, towards Finland and Sweden. As a result, the volatile radioiodine was detected in Lithuania within the first few days after the accident (Mastauskas et al., 1997, Nedveckaite and Filistovic, 1995). The contamination of the Western regions (Western part of Belarus, Poland, and Lithuania) took place on April 26 and 27, 1986. The overall release rate of 131I varied over the first few days following the steam explosion, with a 40 % release on April 26 and an 11.6 % release on April 27 (Nedveckaite et al., 2004). In Lithuania, only dry deposition occurred at the end of April and the beginning of May 1986. The radioiodine activity in the milk consumed by residents of Lithuania showed significant variability. A study conducted in Lithuania following the Chernobyl accident revealed that the concentration of 131I in milk peaked four days after the deposition when cattle were grazing on fresh pasture (a grazing period usually started from the end of April or early May). The effective half-time for the decrease in 131I concentration ranged from 4.2 ± 0.6 days in more contaminated South and Western areas to 5.2 ± 0.9 days in less contaminated areas (Nedveckaite et al., 2004).

Since no direct thyroid activity measurements were performed in Lithuania after the accident (Nedveckaite et al., 1989), the thyroid radiation dose due to 131I intake had to be evaluated indirectly. The internal thyroid dose was mainly due to consuming fresh cow’s milk and, to a lesser extent, green vegetables (IAEA, 2006) and inhalation. Pasture grass and milk contamination measurements have been carried out in almost all regions of Lithuania after the accident till the 19th of May 1986. Measurements of dose rate taken at the altitude of 1 m above the ground surface (mostly due to 131I, 132Te+132I and 133I isotopes) in Vilnius on the first day after the Chernobyl NPP accident showed values ten times higher than usual (Mastauskas et al., 1997, Nedveckaite and Filistovic, 1995). Despite only dry deposition, weather conditions led to different levels of exposure to radioactive fallout in different regions of Lithuania, as the initial cloud passed only over Southern and Western parts of the country.

Averaged age-dependent thyroid doses were estimated for every municipality (district and city). The thyroid dose estimates were obtained based on radioiodine activity in milk, which was reconstructed using data of 131I activity measurements in grass Cmax _grass (Bq/kg f.w.), available almost for all districts of Lithuania (Mastauskas et al., 1997) and normalized to the 2nd of May 1986 (see data in Supplementary Table S1). The reduction of radioiodine activity concentration in plants due to radioactive decay, atmospheric removal from leaf surfaces process (weathering) and growth dilution was considered (Kirchner, 1994, Mastauskas et al., 1997, Nedveckaite and Filistovic, 1995). Radioiodine maximal volumetric activity in milk Cmax _milk (Bq/L) was calculated from the grass activity measurements by using effective coefficient k, relating average activity in milk (Bq/L) to 131I deposition density (Bq/m2), and assuming some average grass yield Y from the cow’s pasture and dry deposition interception factor by grass f:Cmax_milk=k∙Cmax_grass·Yf

where: Cmax _milk – is maximal volumetric activity in milk (Bq/L) on the 2nd of May 1986; Y – is average grass yield from pasture (a single value for whole territory of Lithuania was assumed Y=0.4 kg/m2 (f.w.) as well interception factor f=0.2. The applied values were similar to the ones assumed for Poland (Krajewski et al., 2008). Empirically determined coefficient k values for the low contaminated zone-I of Lithuania were k=0.16±0.04 m2/L and for highly contaminated zone-II k=0.23±0.06 m2/L (Mastauskas et al., 1997, Nedveckaitė et al., 1989).

Measurements of 131I in cow’s milk showed that its concentration was below the permissible levels (370 Bq/L for infants, 3700 Bq/L for the rest of population) only in Lithuania’s central and Northern regions, in contrast to Western and Southern areas where volumetric activity sometimes exceed 1000 Bq/L (Nedveckaite and Filistovic, 1995; Nedveckaite et al., 2004). Therefore, territory of Lithuania was divided into three regions, according to contamination level: 1- clean, 2- intermediate, and 3- relatively highly contaminated (see data in Supplementary Table S1). Based on the time series of the radioiodine activity measurements in milk, the exponential decrease of activity was established. The effective activity decrease rate λoff was evaluated, which differed according to contamination region: λoff=0.13±0.03 d−1 and λoff=0.16±0.03 d−1 for the regions 1, 2 and region 3, correspondingly (Mastauskas et al., 1997, Nedveckaite and Filistovic, 1995). To evaluate thyroid doses due to milk consumption, the integral activity in milk Imilk (Bq·d/L) was assessed. Exponential peak function of milk activity change in time was assumed, based on milk activity measurements in Lithuania (Nedveckaite and Filistovic, 1995). The integral Imilk was calculated for every municipality according to the following expression:Imilk=A∫0∞1−e−tτon∙e−λoff∙tdt=

=Cmax⁡_milk∙1−λoff∙τon1+λoff∙τon∙1λoff+τon1+λoff∙τon∙τon−λoff∙τon

=

where A is a normalizing multiplier term of the assumed exponential peak function, which is related to the measured maximal milk activity Cmax _milk by the following relationship:A=Cmax⁡_milk∙λoff∙1λoff+τon1+λoff∙τon∙τon−λoff∙τon

where, τon is a parameter of activity rise duration to reach the maximum of exponential peak function (d).

The peak of the 131I activity in milk was observed approximately at tmax=3 days after the beginning of rise of milk activity and corresponded to the 2nd of May (Nedveckaite and Filistovic, 1995). Therefore, values of τon=1.8 d and τon =2.3 d were evaluated from the relationship of

tmax=τon∙ln1+1λoff∙τon for the regions 1, 2 and region 3, correspondingly, by considering the region dependent λoff values.

Ingestion dose coefficients were calculated according to the International Commission on Radiological Protection (ICRP) 67 (ICRP, 1993) (see data in Supplementary Table S2). The difference in the milk consumption habits between rural and urban municipalities was not considered in the dose reconstruction and the same average age-dependent milk consumption rates were assigned for both (see data in Supplementary Table S2). Individual data on the consumption habits of the study subjects was unavailable; therefore, average age-dependent average milk consumption of 0.55 L/d for 0–1-year-old babies, 0.6 L/d for 2–16-year-old children, and 0.64 for adults was assumed (Nedveckaite et al., 2004). A dose correction was made for additional 5 % of the inhaled activity of 131I (Drozdovitch V et al., 2010). Since we did not have individual information on breastfeeding, we assumed the same (0.55 L/day) consumption of cow’s milk for all 0–1-year-old babies, as the common practice from the age of 3 months was to supplement mother’s milk with cow’s milk. No radioiodine ingestion with green vegetables was assumed, as consuming wild sorrel or field-grown leafy vegetables was not common at the end of April to the beginning of May in Lithuania.

Since stable iodine distribution was not applied in Lithuania at the time of the accident (in contrast to the neighboring Poland) (Nauman and Wolff, 1993), we did not consider the effect of thyroid blocking.

2.3 Statistical methods

Age-standardized incidence rates were calculated for each calendar year for all ages combined and age-specific rates using the direct method (world standard population). Five-year age categories were used (the lowest group 0–4 and the highest 85+).

Relative risk (RR) analysis was based on three cumulative municipality-specific thyroid dose categories estimated for 0-year-old children at the time of the Chernobyl accident. The reference group consisted of individuals who received less than 100 mGy to their thyroid. The next two groups were considered as “higher-risk individuals,” according to the recommendation of the expert group of the International Agency for Research on Cancer (IARC/WHO) (those exposed in utero or during childhood or adolescence with a thyroid dose of 100–500 mGy (IARC Expert Group on Thyroid Health Monitoring After Nuclear Accidents, 2018)). The second group included residents from the medium dose category region who received a thyroid dose between 100 and 199 mGy; the third group were residents from the most contaminated Western region of Lithuania (high dose category region) who received 200 mGy or more to the thyroid.

Relative risk of thyroid cancer was calculated for two different groups of age at the time of the Chernobyl accident, using 5-year calendar periods and average cumulative municipality-specific dose categories. The analysis was performed using MedCalc version 22.021 (MedCalc Software Ltd) and R version 4.1.0 (R Project for Statistical Computing).

2.4 Ethics

The data were collected in accordance with the Cancer Registry Act, which does not require an informed consent statement or an ethics statement for the analysis of Cancer Registry data.

3 Results

3.1 Thyroid doses

Estimated average thyroid doses due to 131I intake of the Lithuanian inhabitants in all municipalities showed large variation and were depended on age and region of residence. Variation of thyroid doses due to age is caused by different dose coefficients, which are typical for different age groups because of difference in thyroid mass. However, thyroid dose variation among the municipalities was caused by different level of 131I in fallouts.

Fig. 1 shows the entire territory of Lithuania divided into three parts (dose-category regions) depending on the cumulative thyroid dose due to 131I intake at the age 0-year old at the time of the Chernobyl accident.Fig. 1 Lithuanian municipalities, according to the average municipality-specific thyroid doses due to 131I intake at the age of 0 at the time of the Chernobyl accident.

Fig. 1

Thyroid doses for children of different ages, averaged for the three dose-category municipalities, are summarized in Table 1.The average age-dependent thyroid doses (mGy) varied by dose municipality and were notably higher for the youngest children (0 – 2 years), approximately 15 times more than for other age groups. Depending on the municipality contamination level, the thyroid dose estimates for 0-year-old babies ranged from 270 mGy in Western Lithuania to 1.5 mGy in Central and Northern Lithuania. Estimated average age-specific thyroid doses for each municipality are shown in Supplementary Table S3.Table 1 Estimated average age dependent thyroid doses (mGy) by dose region (averaged over the municipalities assigned to the considered region with low/medium/high dose ranges estimated for 0 year old children).

Table 1Thyroid dose range category (region)	Age at the time of the accident (years)	
0	1	2	3	4	5	7	9	10	12	15	18 (adult)	
<100 mGy	15.4	14.9	14.6	12.8	11.2	9.4	7.5	5.7	4.8	4.1	3.1	2.1	
100 −199 mGy	150.6	146.5	142.8	125.8	109.5	92.4	73.9	55.9	46.7	40.2	30.6	20.7	
≥200 mGy	225.6	219.4	213.9	188.5	164.0	138.5	110.8	83.8	69.9	60.2	45.8	31.0	

3.2 Incidence rates

Over the study period (1991–2015), a total of 81.2 million person-years of observation and 5664 cases of thyroid cancer (874 among males and 4790 among females) were registered in the entire Lithuanian population. Thyroid cancer incidence rates were considerably higher among females compared to males, with a ratio of 5:1. Among these, 817 cases were diagnosed in the age group from 0 to 19 years at the time of the Chernobyl accident, and 266 cases in the age group from 0 to 9 years (21.4 and 10.2 million person-years, respectively).

In Lithuania, age-standardized thyroid cancer incidence rates have notably increased since 2000 and reached a peak in 2009, particularly in females, then slightly decreased and stabilized (Fig. 2).Fig. 2 Age-standardised thyroid cancer incidence rates in the whole of Lithuanian population, by sex, 1991–2015.

Fig. 2

Similarly to the entire population, the thyroid cancer incidence rates also started rising after 2000 in the age group of 0–19 years at the time of the accident and increased among both sexes, from 0.05 in 1991–2.52 in 2015 (Fig. 3).Fig. 3 Age-standardised thyroid cancer incidence rates in the age group of 0–19 years at the time of the Chernobyl accident in the whole of Lithuania, by sex, 1991–2015.

Fig. 3

Analysis of the age-standardised thyroid cancer incidence rates by 5-year period among those who were 0–19 at the time of the accident demonstrated similar trends in all three cumulative thyroid dose categories, except the slightly steeper increase observed after 2001 among residents of the most contaminated municipalities (Fig. 4).Fig. 4 Age-standardised thyroid cancer incidence rates in the age group of 0–19 years at the time of the Chernobyl accident by cumulative thyroid dose category.

Fig. 4

We also found that thyroid cancer incidence increased over the study period in the youngest group at the time of the Chernobyl accident (0–9 years), particularly among females, i.e. from 0 in 1991–1.43 in 2015 (Fig. 5).Fig. 5 Age-standardised thyroid cancer incidence rates in the age group of 0–9 years at the time of the Chernobyl accident the whole of Lithuanian population, by sex, 1991–2015.

Fig. 5

Furthermore, in this age group, we compared the thyroid cancer incidence rates between the three cumulative thyroid dose categories (Fig. 6). Although thyroid cancer incidence rates had increased noticeably in the last two observation periods in all three dose categories, a higher increase was observed in the highest dose category in 2011–2015.Fig. 6 Age-standardised thyroid cancer incidence rates in the group of 0–9 years at the time of the Chernobyl accident by cumulative thyroid dose category.

Fig. 6

3.3 Relative risk analyses

In the age group of 0–19 years at the time of the Chernobyl accident, the thyroid cancer relative risk was significantly increased (RR 3.37; 95 % CI: 1.19–8.45, p=0.01) in the highest cumulative dose category, compared to the lowest, in the earliest observation time period (1991–1995), although this observation was based on 7 cases only (Table 2). It remained increased in the following 5-year calendar period but then decreased, with almost no difference observed between the highest and lowest dose categories in the 2011–2015 period.Table 2 Relative risk (RR) of thyroid cancer in the age group of 0–19 years at the time of the Chernobyl accident by 5-year calendar period and average cumulative municipality-specific dose category.

Table 2Period	Dose category (mGy)a	Number of cases	RRb	95 % CIc	p-value	
1991–1995	<100 mGy	18	1			
	100 −199 mGy	5	1.9	0.56–5.36	0.22	
	≥200 mGy	7	3.37	1.19–8.45	0.01	
1996–2000	<100 mGy	37	1			
	100 −199 mGy	5	0.8	0.28–2.30	0.87	
	≥200 mGy	6	1.35	0.46–3.22	0.49	
2001–2005	<100 mGy	145	1			
	100 −199 mGy	10	0.42	0.2–0.8	0.004	
	≥200 mGy	13	0.66	0.35–1.18	0.15	
2006–2010	<100 mGy	261	1			
	100 −199 mGy	22	0.52	0.32–0.80	0.001	
	≥200 mGy	30	0.84	0.56–1.23	0.37	
2011–2015	<100 mGy	328	1			
	100 −199 mGy	43	0.83	0.59–1.15	0.26	
	≥200 mGy	50	1.13	0.82–1.52	0.43	
a mGy – milligray

b RR – relative risk

c CI – confidence interval

In the youngest at the time of the Chernobyl accident age group (0–9 years), due to the small numbers of thyroid cancer cases observed in the higher dose categories, the evaluation was impossible in the earlier study periods, although some tendency of increased RR in the highest dose category appeared in the most recent period 2011–2015 (Table 3).Table 3 Relative risk (RR) of thyroid cancer in the age group of 0–9 years at the time of the Chernobyl accident by 5-year calendar period and average cumulative municipality-specific dose category.

Table 3Period	Dose category (mGy)a	Number of cases	RRb	95 % CIc	p-value	
1991–1995	<100 mGy	5	1			
	100 −199 mGy	1	1.34	0.03–11.96	0.74	
	≥200 mGy	1	1.69	0.36–15.12	0.61	
1996–2000	<100 mGy	9	1			
	100 −199 mGy	0				
	≥200 mGy	0				
2001–2005	<100 mGy	30	1			
	100 −199 mGy	4	0.82	0.21–2.32	0.75	
	≥200 mGy	5	1.24	0.38–3.23	0.63	
2006–2010	<100 mGy	94	1			
	100 −199 mGy	5	0.33	0.10–0.8	0.005	
	≥200 mGy	9	0.7	0.31–1.39	0.31	
2011–2015	<100 mGy	116	1			
	100 −199 mGy	19	1.04	0.61–1.71	0.83	
	≥200 mGy	24	1.51	0.93–2.36	0.07	
a mGy – milligray

b RR – relative risk

c CI – confidence interval

4 Discussion

Our study confirmed the previously observed overall increase in the age-standardised thyroid cancer incidence in the whole Lithuanian population from 2000 onward and continuous stabilization which started around 2010. This observation mirrors the global tendency in trends of thyroid cancer incidence worldwide (Li et al., 2020, Spinelli et al., 2022). Although the problems of overdiagnosis and overtreatment of a disease that, in most cases, is indolent seem to be recognized, the role of other modifiable risk factors for thyroid cancer in the rising incidence of thyroid cancer remains debatable (Kitahara and Sosa, 2016). The exception, perhaps, is exposure to ionizing radiation in childhood and adolescence which has long been the only established modifiable risk factor for thyroid cancer (Dal Maso et al., 2009).

As screening has an impact on the baseline rate of thyroid cancer, it is also an important determinant in the increase of thyroid cancer incidence following nuclear accidents, especially if thyroid screening is differential, i.e., more intensive in the population groups who received higher doses compared to lower or non-exposed (Cléro et al., 2021, IARC Expert Group on Thyroid Health Monitoring After Nuclear Accidents, 2018, Togawa et al., 2018). In Lithuania, there were no screening programs or increased surveillance of thyroid cancer in the areas more heavily affected by the Chernobyl fallout introduced. Our study results are, therefore, not biased by the screening effect.

Despite the small territory, the meteorological conditions at the time of the Chernobyl accident led to a relatively high variation of deposition of 131I over the territory of the Republic of Lithuania. This resulted in quite a wide range of average municipality-specific thyroid doses estimated in our study, particularly in the youngest age group (from 270 mGy in Western Lithuania to 1.5 mGy in Central and Northern Lithuania). The dose estimates did not consider individual milk consumption habits of study subjects, which would have had a decisive role in radioiodine intake and consequently resulted in large uncertainties of the estimated thyroid doses. However, we evaluated typical average thyroid doses for every age category in the municipality assuming average milk consumption rates and taking into account local contamination by 131I in the municipality. This allowed us to identify in Lithuania the group of potentially “higher-risk individuals” (according to the IARC Expert Group on Thyroid Health Monitoring After Nuclear Accidents, 2018 -those exposed in utero or during childhood or adolescence with a thyroid dose of 100–500 mGy) and evaluate the impact of such dose on the risk of thyroid cancer in comparison with those who received less than 100 mGy.

We observed an increase in thyroid cancer risk in the age group 0–19 years at the time of the Chernobyl accident 5–9 years after the accident, which can be related to exposure to radioactive iodine. However, it is based on a small number of observations. We could not confirm this finding in the age group of 0–9 years at the time of the Chernobyl accident because the baseline incidence of thyroid cancer in this age group is very low, and radiation-related excess if it exists, is difficult to detect in such small Lithuanian population. Nevertheless, we observed some tendency of increased risk in the most recent years in the highest exposure category of 0–9 years at the time of accident group, when they became older and the higher baseline thyroid cancer incidence offered more statistical power to detect an increase possibly related to radiation exposure.

A recent study of atomic bomb survivors demonstrated that the excess thyroid cancer risk associated with childhood exposure has persisted for more than 50 years after exposure (Furukawa et al., 2013). It is, therefore, possible that the observed tendency of increased thyroid cancer risk in the most exposed group of the youngest persons could be confirmed if the follow-up is continued.

Our study, although small in size, has several advantages, such as access to the high-quality nationwide population-based cancer registry operating since 1978; available unique data on results of 131I activity measurements in cow’s milk and grass carried out in the entire territory of Lithuania in the first weeks of May which allowed to reconstruct average age-dependent municipality-specific thyroid doses for the entire population; absence of thyroid screening programs that might bias study results.

Limitations of our study are related to the ecological design of the study, i.e., the absence of individual thyroid dose estimates and information about other potential risk factors of thyroid cancer, such as body mass index, smoking, family history of thyroid diseases or iodine deficiency because Lithuania is recognized as a country of mild iodine deficiency (WHO, 2007). It has been reported that the latter has an impact on both – the amount of radioactive iodine absorbed by the enlarged thyroid gland (hence the increased radiation dose because of stable iodine insufficiency in food), and the risk of radiation-induced thyroid cancer (Cardis et al., 2006).

Factors that may have introduced uncertainties in our dose calculation include unavailable information on breastfeeding, source of milk (private cow or commercial) and individual dietary habits, including intake of 131I with green vegetables. The evaluated uncertainty of the average thyroid dose estimates is about ±60 % (SD), obtained as the resulting error of contributing variables (milk consumption rates, 131I activity measurements, λoff, coefficient k, and variation of dose coefficients due to iodine deficiency in the regions).

However, our dose estimates are consistent with the ones obtained by Nedveckaitė et al. (2004). In Nedveckaite et al., 2004, dose coefficients were calculated using the dynamic model and considered the possible effect of stable iodine deficiency. We used age-dependent dose coefficient values from the ICRP 67 publication. Nevertheless, the average estimate of thyroid dose of the 0-year-old baby in the most contaminated region 3 in our study is 104 mGy, which is compatible with the estimates by Nedveckaitė et al. of 158 mGy and 73 mGy, assuming iodine deficiency and sufficiency, respectively. We believe it is a reasonable agreement, as Lithuania is recognised as a county of mild iodine deficiency (WHO, 2007).

Our study contributes to the body of evidence on trends of thyroid cancer incidence, particularly following exposure to low or medium range of doses of radiation in childhood and adolescence. It also informs authorities responsible for preparedness for future nuclear accidents in planning and implementing, when necessary, health monitoring of the most vulnerable population, i.e. children. Although nuclear power plants (NPP) must comply with high safety standards, and the goal of each country is to maintain safe nuclear facilities, history shows that severe nuclear accidents can happen under unexpected circumstances. Currently, a very disturbing situation because of the military conflict at the door of Europe’s largest NPP in Ukraine (i.e. Zaporizhzya NPP) and because of the doubts about compliance with the international safety standards in the Astravets NPP, recently constructed in Belarus, 20 km east of Lithuania and about 40 km from its highly populated capital area (Juozaitis, 2016). A better understanding of the impact of exposure to radiation from the Chernobyl fallout on thyroid cancer helps in guiding preparations for any future nuclear accidents in Lithuania and other European countries.

5 Conclusion

The risk of radiation at low and moderate radiation doses has been increasingly studied over the decades. Our research has led us to conduct a renewed assessment of age-specific thyroid doses, based on the levels of pasture grass and milk contamination that were measured in almost all regions of Lithuania following the Chernobyl accident until May 19, 1986. This allowed us to evaluate a possible association between radiation exposure and the incidence of thyroid cancer, with a particular focus on children and young adults who were residing in the area at the time of the accident. We observed a tendency of increased thyroid cancer risk in the most exposed group of those who were children and adolescents at the time of the Chernobyl accident and resided in western Lithuania, a mostly contaminated part from the Chernobyl fallout. This observation needs to be confirmed by further following trends of thyroid cancer incidence in the cohort of 0–19-year-old Lithuanians at the time of the Chernobyl accident.

Disclaimer

Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization.

CRediT authorship contribution statement

Ausrele Kesminiene: Writing – review & editing, Writing – original draft, Validation, Supervision, Methodology, Investigation, Conceptualization. Giedre Smailyte: Writing – review & editing, Supervision, Methodology, Investigation. Evaldas Maceika: Writing – review & editing, Investigation, Formal analysis, Data curation. Rita Steponavičienė: Writing – review & editing, Writing – original draft, Formal analysis, Conceptualization.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A Supplementary material

Supplementary material

Data availability

Data will be made available on request.

Appendix A Supplementary data associated with this article can be found in the online version at doi:10.1016/j.ecoenv.2024.116789.
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References

But A. Kurttio P. Heinävaara S. Auvinen A. No increase in thyroid cancer among children and adolescents in Finland due to Chernobyl accident Eur. J. Cancer 42 8 2006 1167 1171 10.1016/j.ejca.2006.03.006 16632347
Caini S. Gibelli B. Palli D. Saieva C. Ruscica M. Gandini S. Menstrual and reproductive history and use of exogenous sex hormones and risk of thyroid cancer among women: a meta-analysis of prospective studies Cancer Causes Control 26 4 2015 511 518 10.1007/s10552-015-0546-z 25754110
Cao L.Z. Peng X.D. Xie J.P. Yang F.H. Wen H.L. Li S. The relationship between iodine intake and the risk of thyroid cancer: a meta-analysis Med. (Baltim. ) 96 20 2017 e6734 10.1097/MD.0000000000006734
Cardis E. Kesminiene A. Ivanov V. Malakhova I. Shibata Y. Khrouch V. Drozdovitch V. Maceika E. Zvonova I. Vlassov O. Bouville A. Goulko G. Hoshi M. Abrosimov A. Anoshko J. Astakhova L. Chekin S. Demidchik E. Galanti R. Ito M. Korobova E. Lushnikov E. Maksioutov M. Masyakin V. Nerovnia A. Parshin V. Parshkov E. Piliptsevich N. Pinchera A. Polyakov S. Shabeka N. Suonio E. Tenet V. Tsyb A. Yamashita S. Williams D. Risk of thyroid cancer after exposure to 131I in childhood J. Natl. Cancer Inst. 97 10 2005 724 732 10.1093/jnci/dji129 15900042
Cardis E. Krewski D. Boniol M. Drozdovitch V. Darby S.C. Gilbert E.S. Akiba S. Benichou J. Ferlay J. Gandini S. Hill C. Howe G. Kesminiene A. Moser M. Sanchez M. Storm H. Voisin L. Boyle P. Estimates of the cancer burden in Europe from radioactive fallout from the Chernobyl accident Int. J. Cancer 119 6 2006 1224 1235 10.1002/ijc.22037 16628547
Cléro E. Ostroumova E. Demoury C. Grosche B. Kesminiene A. Liutsko L. Motreff Y. Oughton D. Pirard P. Rogel A. Van Nieuwenhuyse A. Laurier D. Cardis E. Lessons learned from Chernobyl and Fukushima on thyroid cancer screening and recommendations in case of a future nuclear accident Environ. Int. 146 2021 106230 10.1016/j.envint.2020.106230
Dal Maso L. Bosetti C. La Vecchia C. Franceschi S. Risk factors for thyroid cancer: an epidemiological review focused on nutritional factors Cancer Causes Control 20 1 2009 75 86 10.1007/s10552-008-9219-5 18766448
Drozdovitch V. Khrouch V. Maceika E. Zvonova I. Vlasov O. Bratilova A. Gavrilin Y. Goulko G. Hoshi M. Kesminiene A. Shinkarev S. Tenet V. Cardis E. Bouville A. Reconstruction of radiation doses in a case-control study of thyroid cancer following the Chernobyl accident Health Phys. 99 1 2010 1 16 10.1097/HP.0b013e3181c910dd 20539120
Furukawa K. Preston D. Funamoto S. Yonehara S. Ito M. Tokuoka S. Sugiyama H. Soda M. Ozasa K. Mabuchi K. Long-term trend of thyroid cancer risk among Japanese atomic-bomb survivors: 60 years after exposure Int. J. Cancer 132 5 2013 1222 1226 10.1002/ijc.27749 22847218
Greenlee R.T. Hill-Harmon M.B. Murray T. Thun M. Cancer statistics, 2001 CA Cancer J. Clin. 51 1 2001 15 36 10.3322/canjclin.51.1.15 11577478
Howlader, N., Noone, A.M., Krapcho, M., Miller, D., Brest, A., Yu, M., Ruhl, J., Tatalovich, Z., Mariotto, A., Lewis, D.R., Chen, H.S., Feuer, E.J., Cronin, K.A., 2019. SEER Cancer Statistics Review, 1975-2016. National Cancer Institute, Bethesda. 〈https://seer.cancer.gov/csr/1975_2016/〉 (accessed 05.03.24).
IARC Expert Group on Thyroid Health Monitoring After Nuclear Accidents Thyroid health monitoring after nuclear accidents IARC (Int. Agency Res. Cancer) Technical Publication 46 2018 International Agency for Research on Cancer Lyon 〈https://publications.iarc.fr/Book-And-Report-Series/Iarc-Technical-Publications/Thyroid-Health-Monitoring-After-Nuclear-Accidents-2018〉 accessed 05.03.24
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2000. Ionizing radiation, part 1: x- and gamma (γ)- radiation, and neutrons. IARC (Int. Agency Res. Cancer) Monogr. Eval. Carcinog. Risks Hum. 75. International Agency for Research on Cancer, Lyon. https://publications.iarc.fr/93 (accessed 05.03.24).
International Atomic Energy Agency (IAEA), 2006. Environmental consequences of the Chernobyl accident and their remediation: twenty years of experience. Radiol. Assess. Rep. Ser. 8. International Atomic Energy Agency, Vienna. https://www-pub.iaea.org/MTCD/Publications/PDF/Pub1239_web.pdf (accessed 05.03.24).
International Commission on Radiological Protection (ICRP), 1993. Age-dependent doses to members of the public from intake of radionuclides - part 2 ingestion dose coefficients. ICRP Publication 67. Ann. ICRP. 23 (3-4). https://journals.sagepub.com/doi/pdf/10.1177/ANIB_23_3-4 (accessed 17.07.24).
Jacob P. Bogdanova T.I. Buglova E. Chepurniy M. Demidchik Y. Gavrilin Y. Kenigsberg J. Kruk J. Schotola C. Shinkarev S. Tronko M.D. Vavilov S. Thyroid cancer among Ukrainians and Belarusians who were children or adolescents at the time of the Chernobyl accident J. Radio. Prot. 26 1 2006 51 67 10.1088/0952-4746/26/1/003
Juozaitis J. Lithuanian foreign policy vis-à-vis Belarusian nuclear power plant in Ostrovets Lith. Foreign Policy Rev. 35 2016 41 66 10.1515/lfpr-2016-0023
Kirchner G. Transport of iodine and cesium via the grass-cow-milk pathway after the Chernobyl accident Health Phys. 66 6 1994 653 665 10.1097/00004032-199406000-00005 8181940
Kitahara C.M. Sosa J.A. The changing incidence of thyroid cancer Nat. Rev. Endocrinol. 12 11 2016 646 653 10.1038/nrendo.2016.110 27418023
Krajewski P. Ammann M. Bartusková M. Duffa C. Filistovic V. Homma T. Kanyár B. Malátová I. Nedveckaite T. Simon S. Vlasov O. Webbe-Wood D. Zvonova I. Validation of environmental transfer models and assessment of the effectiveness of countermeasures using data on 131I releases from Chernobyl Appl. Radiat. Isot. 66 11 2008 1730 1735 10.1016/j.apradiso.2007.11.022 18541435
Li M. Dal Maso L. Vaccarella S. Global trends in thyroid cancer incidence and the impact of overdiagnosis Lancet Diabetes Endocrinol. 8 6 2020 468 470 10.1016/S2213-8587(20)30115-7 32445733
Mastauskas A. Nedvecktaite T. Filistovic V. Consequences of the Chernobyl accident in Lithuania (IAEA-TECDOC--964(v2)) International Atomic Energy Agency (IAEA) 1997 〈https://inis.iaea.org/collection/NCLCollectionStore/_Public/29/013/29013363.pdf?r=1〉 accessed 05.03.24
Miranda-Filho A. Lortet-Tieulent J. Bray F. Cao B. Franceschi S. Vaccarella S. Dal Maso L. Thyroid cancer incidence trends by histology in 25 countries: a population-based study Lancet Diabetes Endocrinol. 9 4 2021 225 234 10.1016/S2213-8587(21)00027-9 33662333
Nauman J. Wolff J. Iodide prophylaxis in Poland after the Chernobyl reactor accident: benefits and risks Am. J. Med. 94 5 1993 524 532 10.1016/0002-9343(93)90089-8 8498398
Nedveckaite T. Filistovic V. Estimates of thyroid equivalent dose in Lithuania following the Chernobyl accident Health Phys. 69 2 1995 265 268 10.1097/00004032-199508000-00012 7622374
Nedveckaitė T. Filistovic V. Mastauskas A. Thiessen K. Thyroid dosimetry in the western trace of the Chernobyl accident plume Radiat. Prot. Dosim. 108 2 2004 133 141 10.1093/rpd/nch016
Nedveckaitė T. Filistovičius V. Petrulis R. Dauskurdis S. Tamulėnaitė O. Čypas K. Lietuvos TSR kultūrinių ganyklų žolės užteršimo radionuklidais po Černobylio AE avarijos ypatumai. Atmos Fiz 14 1989 80 86
Sali D. Cardis E. Sztanyik L. Auvinen A. Bairakova A. Dontas N. Grosche B. Kerekes A. Kusic Z. Kusoglu C. Lechpammer S. Lyra M. Michaelis J. Petridou E. Szybinski Z. Tominaga S. Tulbure R. Turnbull A. Valerianova Z. Cancer consequences of the Chernobyl accident in Europe outside the former USSR: a review Eur. J. Cancer 67 3 1996 343 352 10.1002/(SICI)1097-0215(19960729)67:3<343::AID-IJC7>3.0.CO;2-R
Shakhtarin V.V. Tsyb A.F. Stepanenko V.F. Orlov M.Y. Kopecky K.J. Davis S. Iodine deficiency, radiation dose, and the risk of thyroid cancer among children and adolescents in the Bryansk region of Russia following the Chernobyl power station accident Int J. Epidemiol. 32 4 2003 584 591 10.1093/ije/dyg205 12913034
Smailyte G. Miseikyte-Kaubriene E. Kurtinaitis J. Increasing thyroid cancer incidence in Lithuania in 1978-2003 BMC Cancer 6 2006 284 10.1186/1471-2407-6-284 17156468
Smittenaar C. Petersen K.A. Stewart K. Moitt N. Cancer incidence and mortality projections in the UK until 2035 Br. J. Cancer 115 9 2016 1147 1155 10.1038/bjc.2016.304 27727232
Spinelli C. Ghionzolli M. Oreglio C. Sanna B. De Napoli L. Morganti R. Antonelli A. Morabito A. Miccoli P. Increased trend of thyroid cancer in childhood over the last 30 years in EU countries: a call for the pediatric surgeon Eur. J. Pediatr. 181 11 2022 3907 3913 10.1007/s00431-022-04596-4 36044066
Steliarova-Foucher E. Colombet M. Ries L.A.G. Moreno F. Dolya A. Bray F. Hesseling P. Shin H.Y. Stiller C.A. International incidence of childhood cancer, 2001-10: a population-based registry study IICC-3 contributors Lancet Oncol. 18 6 2017 719 731 10.1016/S1470-2045(17)30186-9 28410997
Suzuki T. Matsuo K. Hasegawa Y. Hiraki A. Kawase T. Tanaka H. Tajima K. Anthropometric factors at age 20 years and risk of thyroid cancer Cancer Causes Control 19 10 2008 1233 1242 10.1007/s10552-008-9194-x 18618280
Togawa K. Ahn H.S. Auvinen A. Bauer A.J. Brito J.P. Davies L. Kesminiene A. Laurier D. Ostroumova E. Pacini F. Reiners C. Shinkarev S. Thomas G. Tronko M. Vaccarella S. Schüz J. Long-term strategies for thyroid health monitoring after nuclear accidents: recommendations from an Expert Group convened by IARC Lancet Oncol. 19 10 2018 1280 1283 10.1016/S1470-2045(18)30680-6 30303113
United Nations Scientific Committee on the Effect of Atomic Radiation (UNSCEAR), 2022. Sources, effects and risks of ionizing radiation, UNSCEAR 2020/2021 rep. 2. https://doi.org/10.18356/9789210010047.
United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), 2011. Sources and effects of ionizing radiation, UNSCEAR 2008 rep. 2., 45–219. https://doi.org/10.18356/ce8f288a-en.
Vaccarella S. Franceschi S. Bray F. Wild C.P. Plummer M. Dal Maso L. Worldwide thyroid-cancer epidemic? The increasing impact of overdiagnosis N. Engl. J. Med. 375 7 2016 614 617 10.1056/NEJMp1604412 27532827
World Health Organization (WHO), 2007. Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers, 3rd ed. WHO, France. https://www.who.int/publications/i/item/9789241595827 (accessed 10.03.24).
Zupunski L. Ostroumova E. Drozdovitch V. Veyalkin I. Ivanov V. Yamashita S. Thyroid cancer after exposure to radioiodine in childhood and adolescence: 131I-related risk and the role of selected host and environmental factors Cancers 11 10 2019 1481 10.3390/cancers11101481 31581656
