Risk of Thyroid Cancer among Chernobyl Liquidators

RADIATION RESEARCH 178, 425–436 (2012)0033-7587/12 $15.00�2012 by Radiation Research Society.All rights of reproduction in any form reserved.DOI: 10.1667/RR2975.1

Risk of Thyroid Cancer among Chernobyl Liquidators

Ausrele Kesminiene,a,1 Anne-Sophie Evrard,a,2 Viktor K. Ivanov,b Irina V. Malakhova,c Juozas Kurtinaitise,d,3

Aivars Stengrevics,e Mare Tekkel,f Sergei Chekin,b Vladimir Drozdovitch,a Yuri Gavrilin,g Ivan Golovanov,g

Viktor P. Kryuchkov,g Evaldas Maceika,h Anatoly K. Mirkhaidarov,i Semion Polyakov,c Vanessa Tenet,a

Aleksandr R. Tukov,g Graham Byrnesa and Elisabeth Cardisa,4, 5,6

a International Agency for Research on Cancer, Lyon, France; b Medical Radiological Research Centre of Russian Academy of Medical Sciences(MRRC RAMC), Obninsk, the Russian Federation; c Republican Scientific and Practical Center for Medical Technologies, Informatization,

Administration and Management of Health (RSPC MT), Minsk, Belarus; d Institute of Oncology, Vilnius University, Vilnius, Lithuania; e LatvianCentre of Oncology, Riga, Latvia; f National Institute for Health Development, Tallinn, Estonia; g Federal Medical Biological Agency, Burnasyan

Federal Medical Biophysical Centre, Moscow, the Russian Federation; h State Scientific Research Institute Center for Physical Sciences andTechnology, Vilnius, Lithuania; i Republican Scientific Centre of Radiation Medicine and Human Ecology, Gomel, Belarus;

Kesminiene, A., Evrard, A-S., Ivanov, V. K., Malakhova, I. V.,Kurtinaitis, J., Stengrevics, A., Tekkel, M., Chekin, S., Drozdo-vitch, V., Gavrilin, Y., Golovanov, I., Kryuchkov, V. P., Maceika,E., Mirkhaidarov, A. K., Polyakov, S., Tenet, V., Tukov, A. R.,Byrnes, G. and Cardis, E. Risk of Thyroid Cancer amongChernobyl Liquidators. Radiat. Res. 178, 425–436 (2012).

After the Chernobyl accident in 1986, the ‘‘liquidators’’ orclean-up workers were among those who received the highestradiation doses to the thyroid from external radiation. Somewere also exposed to radioiodines through inhalation oringestion. A collaborative case-control study nested withincohorts of Belarusian, Russian and Baltic liquidators wasconducted to evaluate the radiation-induced risk of thyroidcancer. The study included 107 cases and 423 controls.Individual doses to the thyroid from external radiation andfrom iodine-131 (131I) were estimated for each subject. Mostsubjects received low doses (median 69 mGy). A statisticallysignificant dose-response relationship was found with totalthyroid dose. The Excess Relative Risk (ERR) per 100 mGywas 0.38 [95% confidence interval (CI): 0.10, 1.09]. The riskestimates were similar when doses from 131I and externalradiation were considered separately, although for externalradiation the ERR was not statistically significantly elevated.The ERR was similar for micro carcinomas and larger sizetumors, and for tumors with and without lymph node

involvement. Although recall bias and uncertainties in dosescould have affected the magnitude of the risk estimates, thefindings of this study contribute to a better characterizationthe risk of thyroid cancer after radiation exposure inadulthood. � 2012 by Radiation Research Society

INTRODUCTION

Over the last 25 years, there have been many reports ofincreased incidence of cancer and of other health effectsattributed to the Chernobyl accident (1–4). Until now,however, only the dramatic increase in thyroid cancerincidence among those exposed in childhood and adoles-cence has been clearly demonstrated to be related toradiation from the accident (1–8) and, more recently, anincreased risk of leukemia and lymphoma among Chernobylliquidators (9, 10).

While it is well established that exposure to ionizingradiation in childhood and adolescence increases the risk ofthyroid cancer, the effects of exposure in adults remainsambiguous. For external radiation, results from the Japaneseatomic-bomb survivors study suggest that the excess risk ofthyroid cancer after exposure to external radiation atyounger adult ages is smaller than that at age 10 but isstill elevated, especially, if the exposure occurs before age30 (11, 12). Studies of exposure to 131I in adults, in cohortsof patients with therapeutic and diagnostic exposures, havenot provided firm evidence for a radiation-related increasein thyroid cancer, as previously reviewed [see ref. (13) for areview].

A possible association between Chernobyl radiation andrisk of thyroid cancer for those exposed as adults wasstudied in the residents of highly contaminated areas and inliquidators (clean-up workers). No dose-response relation-ship was found in a study that assessed the risk for adultsliving in the contaminated areas of the Bryansk region ofRussia (14). An early study conducted in the contaminated

1Address for correspondence: International Agency for Researchon Cancer, 150 Cours A. Thomas, 69372 Lyon Cedex 08, France; e-mail: [email protected].

2Current address: Epidemiological Research & Surveillance Unit inTransport, Occupation and Environment (UMRESTTE), JointResearch Unit of INRETS (French Research Institute on Transport& Safety), Claude Bernard University of Lyon, and National Institutefor Public Health Surveillance, Bron, France.

3Deceased.4Current address: Center for Research in Environmental Epidemi-

ology (CREAL), Barcelona, Spain.5Municipal Institute of Medical Research (IMIM Hospital del Mar),

Barcelona, Spain.5CIBER Epidemiologia y Salud Publica (CIBERESP), Barcelona,

Spain.

425

regions of Ukraine found no relationship between exposureand increase in thyroid cancer incidence in the exposedadults (15). More recent analyses of thyroid cancerincidence rates in Ukraine from 1989 through 2008 showedsome indication of an excess in thyroid cancer cases inresidents of highly contaminated areas who were exposed asadults, in particular in females (16). These studies, however,suffer from a number of limitations, including lack ofadequate dosimetry, ecological biases and limitations, andtheir findings are difficult to interpret with certainty. Amongliquidators, an increased incidence of thyroid cancer hasbeen reported in a number of cohorts from Belarus, Russiaand Ukraine (17–19) compared to the general population ofthese countries. Most recently, based on a small number ofcases, an increase was also reported in a combined cohort ofliquidators from Estonia and Latvia (20). Because Cher-nobyl liquidators tend to undergo a more intensive medicalsurveillance than the general population (21, 22), it isunclear whether these increases reflect a real associationrelated to radiation exposure or an artifact due to asurveillance bias. In a study of 99,024 liquidators from 6regions in Russia (23), the risk of thyroid cancer wasevaluated by the level of radiation dose, thus reducing theimpact of a potential surveillance bias. No associationbetween radiation dose and risk of thyroid cancer was foundin the study in which officially recorded external radiationdose estimates were used. These dose estimates, however,are known to be inaccurate (2, 24). Additionally, noinformation on dose from other radiation types wasavailable.

Liquidators were mainly exposed to external penetrating cradiation. Internal exposure due to ingestion was lessimportant, though inhaled radioiodines may have contrib-uted to the dose for a small proportion of those who workedin the first weeks after the accident. In the first few daysafter the accident, dose rates were extremely heterogeneousand the liquidators who worked on the industrial site of theChernobyl nuclear power plant, as well as those whoresided in the most contaminated areas of Belarus, couldhave received very high doses (up to several Gy) (2).

We therefore conducted a collaborative study amongliquidators from Belarus, Russia, Estonia, Latvia andLithuania with the objective of evaluating more preciselythe relationship between the dose to the adult thyroid fromboth external c radiation and internally incorporatedradioiodines and risk of thyroid cancer. A secondaryobjective was to assess the role of screening in the observedincreased thyroid cancer incidence among Chernobylliquidators.

MATERIALS AND METHODS

Study Design and Collection of Information

The study was designed as a case-control study nested withincohorts of liquidators who worked on the industrial site and in themost contaminated areas around the Chernobyl nuclear power plant

between April 26, 1986 and December 31, 1987. As described indetail elsewhere (9), the study population consisted of approximately66,000 Belarusian, 65,000 Russian and 15,000 Baltic countryliquidators identified through the national Chernobyl Registries inBelarus and Russia, and through the rosters of the established Balticliquidator cohorts. The cohorts of Baltic liquidators were establishedin the 1990s and verified for completeness using several sources (28).Although there are concerns about the completeness and accuracy ofregistration of liquidators in the Chernobyl registries of Belarus andRussia, and further information should be collected in case-controlstudies to verify the status of the liquidators, these registries provide areasonable roster for more detailed studies of long-term health effectsof the Chernobyl accident (3).

In the Belarusian cohort and the Russian sub-cohort of professionalradiation workers, the proportion of women liquidators was quitesubstantial. Because the background thyroid cancer incidence amongwomen is higher than among men (25), and because any potentialmodifying effect of gender on the radiation-induced thyroid cancerrisk is not very clear (4), we decided to include both men and womenfrom these cohorts.

The cases were defined as all histologically verified cases ofpapillary or follicular carcinoma diagnosed in the study populationduring the study period: 1993–1998 for Russia; 1993–2000 forBelarus; and 1990–2000 for Baltic countries. Cases were ascertainedretrospectively from the national population based cancer registries inBelarus, Estonia, Latvia and Lithuania (26), and from the NationalMedical Dosimetry Registry (NMDR) in Russia. The population-based cancer registries in Belarus and the Baltic countries have existedsince the 1970s, but individual patient records became available sincethe 1980s. The registries contributed cancer incidence data to theCancer Incidence in Five Continents starting from volume VI (27).This facilitated verification of completeness of case ascertainment. InRussia, a computerized cancer registration system, the NationalMedical Dosimetry Cancer sub-registry, was established in the 1990sfor the groups of populations affected by the Chernobyl accidentincluding liquidators and residents of the most contaminated regions.It collects personalized information on incident cancer cases amongliquidators (28).

From 1997, shortly after the current study started, prospective caseascertainment was conducted in Belarus and Russia through the majorendocrinological and/or surgical departments of the oblast (adminis-trative region) and central hospitals in Minsk (Belarus), St. Petersburgand Moscow (Russia) where all patients with preliminary diagnosis ofthyroid cancer are referred for confirmation and treatment. Collabo-ration was established with these treatment institutions for the purposeof the current study to ensure rapid reporting to the national studycoordinators about newly diagnosed cases of thyroid cancer inliquidators.

To maximize statistical power, four controls were selected, using arandom number generator from the roster of the study population ineach country (i.e., from the Chernobyl Registries in Belarus andRussia, and from electronic lists of the established cohorts in Balticcountries). They were matched on age, sex and region of residence atthe time of the accident in Belarus and Russia, and on age and countryin Baltic countries.

A trained interviewer collected information on the history andconditions of work as a liquidator (places, dates, duration, protectivemeans, type of activities and residence) during a face-to-face interviewwith the study subject. The detailed questionnaire also containedquestions about demographic factors, history of occupational andmedical radiation exposures, personal and family history of cancer andof thyroid diseases, smoking and alcohol consumption.

Verification of Diagnoses

An international panel comprised of Belarusian, Russian andFinnish pathologists reviewed histological slides of the case patients

426 KESMINIENE ET AL.

included in the study. For logistical reasons, slides were not availablefor review for 22% of cases. Since the proportion of cases for whichthe original diagnosis was contradicted by the international panel wasvery small (1%), the main analyses included all of the cases, whetheror not their diagnosis could be verified. Sensitivity analyses were alsoconducted and were used to exclude cases with unverified diagnoses.

Radiation Dose Estimation

For each study subject, individual doses to the thyroid werereconstructed by considering the following pathways of exposure: (1)external irradiation from c-ray-emitting radionuclides; and (2) internalirradiation arising from the intake of 131I via inhalation ofcontaminated air or ingestion of contaminated foodstuffs.

To estimate external doses received by the liquidators during theirclean-up missions, a method entitled RADRUE (Realistic AnalyticalDose Reconstruction with Uncertainty Estimation) was developed andvalidated by a multinational group of dosimetrists and epidemiologists(29). Results of exposure rate and nuclide deposition measurementswere embedded in RADRUE and were used to derive exposure-ratesat places where liquidators lived and worked, and thus to calculateexternal dose to the thyroid according to the liquidators’ itineraries.Liquidators’ routes were reconstructed by dosimetry experts familiarwith the organization and conditions of work in the 30-km zone basedon information obtained through the study questionnaire. The methodis described in detail elsewhere (29).

Internal doses to the thyroid due to the intake of 131I via inhalationduring the period of work as a liquidator were calculated for the sixstudy subjects who worked on the industrial site during the first 2weeks after the accident. The approach was based on themeasurements of concentration of 131I in air in the settlements in the30-km zone (30). It was assumed that activity of 131I inhaled by theliquidators who worked at the Chernobyl NPP site, as well as insidebuildings of the Chernobyl NPP, correlated with the dynamics ofconcentration of 131I at locations close to the Chernobyl NPP. Thisapproach was validated by measurements of the dose-rate near theneck taken, April 30, 1986 through May 5, 1986 in a group of 624early liquidators. For this purpose, values of 131I activity in the thyroidswere calculated with the approach used in our study and thencompared with those derived from the direct thyroid measurementstaken in 1986. The mean of ratios of those measured to calculatedactivities was found to be 0.8 6 1.1 and the median of ratios was 0.5.The modeled doses from 131I inhalation for the study subjects werethen calibrated against the median of ratios of those measured tocalculated 131I activity in the thyroids of the group of 624 liquidators.

In addition to the dose received during their work, liquidators whowere residents of contaminated settlements of Gomel and Mogilevoblasts of Belarus and were returning home every evening or afterweekly shift-work may also have received substantial dose to thethyroid from 131I through consumption of locally produced contam-inated milk and/or vegetables, and also from external irradiation fromground deposits of gamma-ray-emitting radionuclides. For theseliquidators, ‘‘residential’’ doses from 131I were estimated up to June20, 1986 and from external irradiation—for the entire period of workas a liquidator using models previously developed for calculatingaverage doses to the thyroid in contaminated settlements of Belarus(31, 32). No information was collected in our study about individualconsumption of milk and leafy vegetables around the time of theaccident. The estimated residential component of the total dosetherefore represents average doses in each subject’s settlement ofresidence. Some of the study subjects from Belarus lived in 42settlements where direct measurements of 131I activity in the thyroidsof residents were performed in May and early June of 1986. Wecompared the residential thyroid doses reconstructed within our studywith the mean thyroid doses in the settlements of residence derivedfrom direct thyroid activity measurements. The mean of ratios ofthyroid dose from 131I intake estimated using the model to that

estimated from the direct thyroid measurement was 1.8 6 1.2 and themedian of ratios was 1.5.

Residential doses were not calculated for Russian and Balticliquidators as they were thought to have consumed foodstuffs thatwere produced in and imported from uncontaminated areas duringtheir work in the Chernobyl area, and as levels of 131I in their originalplaces of residence were substantially lower than in the mostcontaminated districts of the Gomel and Mogilev regions in Belarus.

Intake of short-lived radioactive iodine isotopes was considered tobe negligible for all except one study subject, who started to work onApril 26, 1986 on the industrial site of the Chernobyl nuclear powerplant. For that liquidator thyroid dose was estimated to be mainly dueto the inhalation of 131I, with a contribution from short-livedradioiodines and 132Te [estimated using the approach developed forthe population of the 30-km zone around the Chernobyl nuclear powerplant (32)], not exceeding 35% of the total thyroid dose.

For the purpose of the current study, the total radiation dose to thethyroid was estimated in mGy as the sum of the doses from externalexposure and from intake of 131I, short-lived radioiodines, and 132Teduring their clean-up mission for Russian and Baltic liquidators.Residential doses from 131I and external radiation were added for theirBelarusian counterparts.

Uncertainties in radiation dose estimates were evaluated as a part ofthe dose reconstruction process. The major sources of errors werefound to be the errors related to the parameters of the dosimetry modeland to the information obtained by questionnaire through the personalinterviews (29). Errors from these sources were characterized andquantified. By the application of Monte Carlo simulations, a set of10,000 approximately log-normally distributed dose estimates wasobtained for each subject and for the major dose components (externaldose and residential 131I dose). The geometric standard deviation(GSD) of the external doses varied from 1.1 to 5.8 with a median equalto 1.8, while for the residential doses from 131I intake GSD varied from1.9 to 2.5 with a median of 2.0.

The assumption was made that doses from external radiation and131I were independent as the approach used to estimate these differedconsiderably and because little correlation was found between centraldose estimates from both sources (Pearson correlation coefficient:�0.052. Spearman rank correlation coefficient: 0.035). For Belarusianliquidators who also received residential doses, shared errors withinthe same mission and within the same settlement of residence werealso evaluated, but not across missions or residences.

Consent and Approval

Written informed consent to participate in the study was obtainedfrom each study subject, as appropriate. The study was approved bythe IARC Ethical Review Committee, the Belarus CoordinatingCouncil for Studies of the Medical Consequences of the ChernobylAccident, the Ethical Committee of the Medical RadiologicalResearch Centre of the Russian Academy of Medical Sciences,Obninsk, the Ethical Review Board of the Institute of Oncology,Vilnius, Lithuania, the Ethical Review Committee of LatvianOncology Center, and the Tallinn Medical Research Ethics Commit-tee. The procedures followed were in accordance with the ethicalstandards of the responsible committee on human experimentation(institutional or regional) and with the Helsinki Declaration of 1975,as revised in 1983.

Statistical Methods

Data were analyzed by conditional logistic regression using thePECAN module within the EPICURE software package (33). Twodifferent risk models were fitted as follows. The primary risk modelused was the linear Excess Relative Risk (ERR) model, which is themodel most commonly used in radiation epidemiology (34). The oddsratio (OR) at a dose d approximates the estimate of the relative risk

THYROID CANCER AMONG CHERNOBYL LIQUIDATORS 427

(RR) for rare diseases such as thyroid cancer and is expressed asOR(d)¼1 þ b d þ c d2 þ . . . , where b and c denote, respectively, theslope coefficients of the linear and quadratic dose terms in the model.Analyses were also carried out with the model most generally used inoccupational and environmental epidemiology (35), the log-linear riskmodel, in which the odds ratio at a dose d is expressed as OR(d) ¼exp(b d þ c d2 þ . . . ). As can be seen below, within the range ofdoses in the data set, both risk models yielded very similar riskestimates. However, the ERR model is frequently unstable for theestimation of relatively small risks associated with relatively lowdoses, particularly when the number of subjects is small. Thus,convergence problems are sometimes encountered in fitting thismodel. Consequently, the log-linear risk model was used for theexploration of interactions, especially when looking at effectmodification.

The main analyses included dose as a continuous variable.Departures from linearity of risk were explored by fitting polynomialequations in dose. In addition, departures from a constant relative riskmodel were explored by carrying out analyses that addressed thepossible modifying effects of other variables (including country,gender, age at exposure, time since exposure, attained age and dose-rate) by the introduction of interaction terms between the factorconsidered and the radiation dose in the log-linear risk model. Thestatistical significance of model parameters was tested with thelikelihood ratio test. All statistical tests were two-sided.

The effect of potential confounders (including education, occupa-tion at the time of the Chernobyl accident, organization that sent theliquidator to Chernobyl and other known or suspected risk factors forwhich information was collected in the questionnaire) was tested byintroducing them in the statistical analyses. A factor was taken to be aconfounder of the association between radiation dose and the risk ofthyroid cancer if it modified the OR by 10% or more.

Analyses were also conducted using dose as a categorical variablein six distinct categories (0, 68.8, 100, 200, 300 and 400 mGy). Thereference category included all subjects whose dose was below themedian of the dose distribution, and the upper categories were chosento span the width of this skewed distribution. Estimated odds ratiosand confidence intervals were calculated for the mean of each doseclass.

In the main analyses, we included only the liquidators whose dosewas estimated with RADRUE from the interview completed by theliquidator himself or by a colleague proxy (these were more accuratethan those completed by a relative proxy). We also excluded from themain data set four cases (and their respective controls) of medullarythyroid carcinoma that was considered unlikely to be caused byradiation and a follicular tumor with an uncertain grade of malignancyas defined by the International Panel. Sensitivity analyses wereconducted to evaluate the robustness of the findings to these analyticalchoices.

Effect of Uncertainties in the Dose Estimates

The dose-response estimate and its confidence limits were estimatedusing a maximum likelihood approach incorporating the uncertainty ofthe assigned doses. The likelihood for any given set of doses can beevaluated by standard methods. However, to account for theuncertainty of the dose estimates it is necessary to integrate over allpossible dose assignments, weighted by their probabilities and given ahypothetical true dose assignment (36). This process was approxi-mated by making 10,000 draws from a Bayesian posterior distributionof the doses, using the Monte Carlo Maximum Likelihood approach(37, 38). Although the null distribution of the likelihood ratio (LR)statistic does not necessarily have the standard v2 distribution, weconducted simulations to validate the process for the range of doses inthe present study. The central estimate of the dose-response was thenobtained by maximizing this Monte Carlo likelihood with respect tothe dose-response parameters. Conceptually, this is the same as in

standard maximum likelihood estimation, although the numericalcomputation is somewhat more involved. The confidence set isdefined as all dose-response curves that would not be rejected as asignificantly worse fit than the maximum likelihood estimate, usingthe LR test. We identified the upper and lower envelope of a sample ofthese curves as the confidence set boundaries.

RESULTS

Descriptive Analyses

A total of 127 eligible case patients were ascertainedretrospectively and prospectively. Four cases were diag-nosed with medullary carcinoma and 122 as papillarycarcinomas. For the remaining case, the International Panelof pathologists suspected a diagnosis of follicular carcino-ma, but could not confirm this with certainty due to poorquality of pathological material. As explained above, thiscase and the four cases of medullary carcinoma and theircontrols were excluded from the main analyses.

Ten case patients or proxies of deceased patients refusedto participate in the study; two patients could not be tracedand interviewed. Participation rates were generally highamong cases—78% in Baltic countries, 94% in Russia, 89%in Belarus and were somewhat lower among controls—65%in Baltic countries, 91% in Russia and 82% in Belarus.Overall, 107 case patients and 423 control subjects wereincluded in the study after exclusion of 3 deceased caseswhose dose was estimated based on the interview completedby a relative less familiar with the liquidator’s work inChernobyl than would have been a proxy who was acolleague. The majority of case patients (85) were fromBelarus, the rest (15 and 7, respectively) were from Russiaand the Baltic countries (Table 1).

Overall, the median age at the moment of first exposurewas 37 years old and at the time of diagnosis was 45 yearsold (Table 1). There were more cases diagnosed withthyroid cancer at 50 years old and older in the more recentperiod (after 1996) compared to the earlier period.Belarusian study subjects differed substantially from theRussian and Baltic subjects (Table 2). The proportions ofmen (53%) and women (47%) were similar in Belarus,while most liquidators in Russia (94%), and all liquidatorsin Baltic countries were men. Ninety percent of Belarusliquidators were sent on clean-up missions by civilianorganizations (while Russian and Baltic liquidators weremainly military reservists), 39% did not work in the 30-kmzone (5% and 3%, respectively, among Russians and Balticliquidators), only 2.1% reported having worked on theindustrial site of the Chernobyl power plant (68% and 73%,respectively, among Russians and Baltic liquidators), and23% were sent on two missions or more (only one Russiancase patient had more than one mission). Only 6% ofRussian liquidators started work before May 10, 1986,compared to 35% in Belarus and 15% in Baltic countries.No difference in the distribution of date of start of missionbetween cases and controls was seen, although in all


countries the median date of start of case patients was earlier

than that of controls (Table 2). The median number of

working days for all missions was shorter (Table 2) in

Belarus than elsewhere (21.5 days in Belarus, 61.0 in Russia

and 75.0 in Baltic countries). Case patients and controls did

not differ notably in median number of working days,

except in the Baltic countries where controls tended to have

more active days (days spent in the Chernobyl zone

excluding resting periods) (median: 83.0) than case patients

(median: 65.0).

No differences in the distribution of the potentially

confounding factors, such as education level, family status,

TABLE 1Characteristics and Distribution of Study Case Patients by Country

Characteristic

Total Belarus Russia Baltic countries

n ¼ 107 n ¼ 85 n ¼ 15 n ¼ 7

Number % Number % Number % Number %

By genderMale 66 62 45 53 14 93 7 100Female 41 38 40 47 1 7 0

By age at exposure,35 45 42 37 44 7 47 1 1435–49 49 46 35 41 8 53 6 8650þ 13 12 13 15 0 0 0 0Median 37 37 36 39Range 17–60 17–60 19–45 32–44

By age at diagnosis,35 11 10 9 10 2 13 0 035–49 52 49 38 45 10 67 4 5750þ 44 41 38 45 3 20 3 43Median 45 46 43 48Range 27–72 27–72 28–53 44–57

TABLE 2Distribution of Cases and Controls by Characteristics of Mission

Characteristic

Total Belarus Russia Baltic countries

Cases Controls Cases Controls Cases Controls Cases Controls

Did the subject work in the 30-km zone?Yes (inside) 73 289 52 205 14 59 7 25

% 68 68 61 61 93 95 100 96No (outside) 34 134 33 130 1 3 0 1

% 32 32 39 39 7 5 0 4P-homogeneitya 1.00 1.00 1.00 1.00Date of beginning of mission

Before June 20, 1986 63 224 55 203 3 11 5 10% 59 53 65 61 20 18 71 38

June 20–August 31, 1986 19 63 17 52 2 6 0 5% 18 15 20 16 13 10 0 19

September1, 1986–December 31, 1987 25 136 13 80 10 45 2 11% 23 32 15 24 67 73 29 42

P-homogeneitya 0.19 0.19 0.72 0.31Median 25/05/86 11/06/86 15/05/86 03/06/86 22/12/86 06/01/87 12/05/86 11/07/86Number of active working days for all missions in Chernobyl

,12 days 26 104 25 102 1 2 0 0% 24 25 29 30 7 3 0 0

12–30 days 23 108 21 102 2 6 0 0% 21 26 25 30 13 10 0 0

31–86 days 30 105 17 57 8 35 5 13% 28 25 20 17 53 56 71 50

86 days þ 28 106 22 74 4 19 2 13% 26 25 26 22 27 31 29 50

P-homogeneitya 0.81 0.67 0.74 0.41Median (days) 32 30 25 21 62 61 65 83

a Fisher’s exact test.


past occupational exposure to radiation, history of cancer,smoking and alcohol consumption, were observed betweencase patients and controls (Table 3). However, case patientssignificantly differ from controls in respect to the pastmedical radiation exposure, history of thyroid diseases andstable iodine prophylaxis (Table 3). Case patients morefrequently reported having thyroid disease in the past orundertaken stable iodine prophylaxis, but were less frequent-ly exposed to medical radiation compared to controls.

The distribution of total thyroid radiation doses wasskewed for all subjects (Fig. 1). The median radiation dosefrom all radiation types was estimated to be 70.4 mGy inBelarus, 63.0 mGy in Russia and 55.5 mGy in Balticcountries; the range of doses was, however, much wider inBelarus. The median doses received by female liquidatorswho were mainly Belarusian were higher (196.1 mGy) thanthose received by males (63.8 mGy). The major contribu-tion to the total thyroid dose for Belarusian liquidators wasfrom exposure to 131I in their place of residence.

The median radiation dose from all radiation types tendedto be higher among case patients than among controlsoverall in Belarus and in the Baltic countries (Table 4), butnot in Russia. The median thyroid dose from exposure to131I was much higher for Belarusian liquidators (Table 4)than in other countries, mainly reflected doses received attheir places of residence from consuming contaminated milkand leafy vegetables, while the median dose to the thyroidfrom external exposure was much lower (6.53 mGy inBelarus, 63.0 mGy in Russia and 55.1 mGy in Balticcountries). In Belarus, doses from external exposure tendedto be similar among men and women (median: 6.34 vs. 8.63mGy, respectively) while average doses from 131I weremuch higher among women than among men (median:260.9 vs. 72.0 mGy), most likely because women werestaying at the site only during the day in the Chernobylzone. They were returning home in the evening where theyreceived higher residential doses from ingestion of contam-inated foods compared to the small doses received by maleliquidators closer to the rector site through inhalation. Incontrast, in Russia, doses from external exposure receivedby male liquidators were considerably higher than thosereceived by the few female liquidators whose activities werelimited to the tasks performed in less contaminated places(canteens, medical aid stations, etc.) (Table 4).

All study subjects received their doses at low dose-rates:only 5 subjects had dose-rates above 25 mGy/day and 7subjects had dose-rates between 10–25 mGy/day at somepoint during their mission.

Risk Analyses

Figure 2 shows the variation in the odds ratio as afunction of dose level. A statistically significant dose-response relationship was observed (P ¼ 0.0008). Theincrease was statistically significant in the penultimate(300–399 mGy: OR 4.20, 95% CI 1.62, 10.9) and highest(400þ mGy OR 2.63, 95% CI 1.36, 5.09) categories.

The ERR/100 mGy was 0.38 (95% CI 0.10, 1.09) overall(Table 5), corresponding to an RR of 1.38 at 100 mGy.There was no evidence of heterogeneity of risk acrosscountries. The ERR/100 mGy was significantly elevatedoverall and especially in Belarus (0.37, 95% CI 0.08, 1.21).The corresponding estimates using the log-linear modelwere lower, except in Russia, and were significantlyelevated overall and in Belarus.

TABLE 3Distribution by Potentially Confounding Factors and by

Case-Control Status (all Countries)

Characteristic

Cases Controls

n % n %

Family statusMarried 89 83 327 77Single 4 4 13 3Widowed 9 8 37 9Divorced 5 5 46 11P-homogeneitya 0.24

Education levelEight class or less 18 17 81 19High school 26 24 138 33Special high school 38 36 131 31Higher school 25 23 72 17Missing 0 0 1 0P-homogeneitya 0.28

Past occupational exposure to radiationYes 10 9 22 5No 97 91 399 94Missing 0 0 2 0P-homogeneitya 0.2

Past medical radiation exposureYes 84 79 353 83No 19 18 67 16Missing 4 4 3 1P-homogeneitya 0.05

Past history of thyroid diseasesYes 59 55 100 24No 45 42 319 75Missing 3 3 4 1P-homogeneitya ,0.001

Stable iodine prophylaxisYes 29 27 77 18No 68 64 325 77Missing 10 9 21 5P-homogeneitya 0.02

Smoking statusb

Current 33 31 173 41Past 10 9 38 9Non smoker 64 60 212 50P-homogeneitya 0.15

Alcohol consumptionYes 79 74 344 81No 28 26 77 18Missing 0 0 2 0P-homogeneitya 0.13

aFisher’s exact test.bSubjects who were smokers and for whom it was not possible to

determine whether they had quit smoking before the reference date areincluded as current smoker in this analysis—results including thesesubjects as ex-smokers are very similar.


The ERR/100 mGy for females was higher (Table 5) thanit was for males, although the difference was not significant.However, the corresponding estimates using the log-linearmodel were very similar.

Analyses by tumor diameter (,10 mm vs. 10 mm ormore) gave similar risk estimates as did analyses with orwithout lymph node involvement.

Risk estimates by type of radiation dose are also shown inTable 5. Risk estimates were similar for 131I and for externalexposure, though the increase was significant only for totaldose and dose from 131I. There was little correlation betweeninternal and external doses (not shown). Adjusting for doses

from external radiation had no effect on the 131I risk

estimate. Adjusting for 131I exposure somewhat reduced the

risk estimate from external radiation when using the linear

ERR, but not when using the log-linear model.

Higher risk estimates were seen among subjects with

dose-rates of 10 mGy/day or more compared to lower dose-

rates, although based on small numbers of subjects.

Results of Sensitivity Analyses

We conducted sensitivity analyses to evaluate the

robustness of the overall risk estimates to different analytic

FIG. 1. Distribution of total thyroid dose among study subjects (overall, by country and by case-control status).


strategies and to different dose estimates. The results of log-

linear analyses were generally similar to those reported

above; as were results using the linear ERR model.

Restricting analyses to subjects who worked in the 30-km

zone, using doses without application of dose-limitation

procedure or unconditional logistic regression yielded

lower, but statistically significantly elevated risk estimates

(not shown). Modeling uncertainties in external dose

estimates had little effect on the risk estimate, although it

increased the width of the confidence interval (Table 5).

Age at exposure and time since exposure did not appear to

modify the association between radiation dose and risk of

thyroid cancer (not shown).

None of the other factors studied such as date of start of

mission, work on roof of reactor, stable iodine prophylaxis,

past medical exposures to radiation, smoking and alcohol

consumption, as well as organization that sent the

liquidators to Chernobyl, number of working days for all

missions, personal monitoring of dose, use of protective

measures, education, marital status, history of cancer or of

thyroid diseases (not shown) appeared to play a role either

as a confounder or as a modifier of the association between

radiation dose and risk.

DISCUSSION

This study is the first study of thyroid cancer in

Chernobyl liquidators in which careful individual thyroid

dose reconstruction was attempted and in which information

was sought on a number of potential risk factors. Overall,

107 case patients and 423 controls from Belarus, Russia and

Baltic countries were included in these analyses. A

significant dose-response relationship was observed be-

tween radiation dose to the thyroid received in adulthood

and the risk of subsequent thyroid cancer, with a

significantly increased risk at doses of 300 mGy or above.

Are the findings of our study unexpected? Table 6 shows

a comparison of the risk estimates in this study with those

derived from analyses of adult atomic bomb survivors (39,40), from the 15-country nuclear industry study (41) and

from the third analysis of the UK NRRW (42), as well as

from studies of exposure to 131I in children and adults (5,43–46). Risk estimates from the current study are higher

than those seen in other populations exposed in adulthood,

except in the UK NRRW study, but are lower than

comparable estimates derived from studies of thyroid cancer

in young people after the Chernobyl accident (5). However,

one should be careful when comparing the magnitude of

risk from exposure to ionizing radiation between popula-

tions that differ in respect to genetic background or

environmental factors, such as stable iodine intake. Iodine

deficiency was present at the time of the Chernobyl accident

in many areas of the former Soviet Union, particularly in

TABLE 4Distribution of Doses to the Thyroid by Country, by Sex and by Case/Control Status

Total Belarus

Cases Controls Cases Controls

Median and range of total dose to the thyroid (mGy)Overall 103 (0.18–3308) 66 (0.13–1643) 153 (0.95–3308) 68 (0.29–1643)Male 69 (0.18–3308) 63 (0.29–924) 69 (3.34–3308) 64 (0.29–924)Female 303 (0.95–1547) 139 (0.13–1643) 306 (0.95–1547) 156 (0.29–1643)

Median and range of external dose to the thyroid (mGy)Overall 13 (0.18–496) 9 (0.11–508) 9 (0.39–142) 6 (0.11–454)Male 22 (0.18–496) 11 (0.11–508) 9 (0.39–142) 6 (0.11–454)Female 9 (0.71–64) 6 (0.11–91) 9 (0.71–64) 6 (0.11–91)

Median and range of internal dose to the thyroid from 131I (mGy)Overall 62 (0–3253) 62 (0–1552) 131 (0.24–3253) 62 (0–1552)Male 18 (0–3253) 8 (0–902) 62 (1–3253) 57 (0–902)Female 287 (0–1517) 123 (0–1552) 291 (0.24–1517) 143 (0–1552)

By sourceMission 0.72 (0–3198) 0.05 (0–1552) 4.27 (0–3198) 1.27 (0–1552)Residence 43 (0–725) 37 (0–734) 62 (0–725) 56 (0–734)

FIG. 2. Comparison of odds ratios (ORs) predicted by different riskmodels with categorical odds ratios estimated in six dose categories:(u) OR and 95% CI; (—), (heavy line) Log-linear model–linear dose-response; (—) (light line) Excess relative risk (ERR) model–lineardose-response.


Belarus (47) and might have modified the effect of radiation

on the risk of thyroid cancer (4).

Uncertainties in thyroid dose estimates and possible

biases resulting from screening, selection, recall, confound-ing, or effect modifiers must be considered carefully in

evaluating the results of this study.

Within this project, considerable efforts were made to

evaluate, quantify and take into account the uncertainties in

thyroid dose estimates. As indicated above, adjustment for

dosimetric uncertainties had little impact on the risk

estimates in this study. However, residential 131I doses for

Belarusian liquidators were estimated crudely and were

based on average doses in the settlement of residence,

because no information had been collected in the question-

naire about consumption of milk and leafy vegetables

around the time of the accident. It is therefore likely that

there is some misclassification of residential 131I doses, but

this should not be differential between cases and controls.

Non-differential misclassification would tend to bias risk

estimates toward the null (48).

A higher risk (although not statistically significantly

different) was observed in female liquidators from Belarus

who were residents of the contaminated villages. Women

received higher doses to the thyroid from 131I compared to

their male colleagues through the ingestion of contaminated

food consumed every day after returning home from work.

Male liquidators who were the residents of contaminated

villages in Belarus were often sent for clean-up activities

during weekdays and returned home only on weekends or

after two-week shifts. During weekdays, they consumed

TABLE 4Extended

Russia Baltic countries

Cases Controls Cases Controls

61 (0.18–496) 66 (0.13–508) 69 (22–323) 41 (1.91–488)79 (0.18–496) 77 (1.94–508) 69 (22–323) 41 (1.91–488)34 (34–34) 3.08 (0.13–4.22) 0 0

61 (0.18–496) 66 (0.13–508) 68 (22–322) 41 (1.91–488)79 (0.18–496) 77 (1.94–508) 68 (22–322) 41 (1.91–488)34 (34–34) 3.08 (0.13–4.22) 0 0

0 (0–1.6) 0 (0–11) 0.39 (0–1.09) 0 (0–1.39)0 (0–1.6) 0 (0–11) 0.39 (0–1.09) 0 (0–1.39)0 (0–0) 0 (0–0)

0 (0–1.6) 0 (0–11) 0.39 (0–1.09) 0 (0–1.39)

TABLE 5Risk Estimates of Thyroid Cancer, from the Linear ERR and Log-Linear Models

Cases/controls

Linear ERR model Log-linear model

ERR/100 mGy 95% CI RR at 100 mGy RR at 100 mGy 95% CI

Overall 107/423 0.38 0.10 1.09 1.38 1.17 1.06 1.29Country-specific

Belarus 85/335 0.37 0.08 1.21 1.37 1.16 1.05 1.29Russia 15/62 0.47 –0.12 5.61 1.47 1.44 0.86 2.47Baltic countries 7/26 0.25 nda nda 1.25 1.12 0.45 2.22

P-homogeneity between countriesb 0.98 0.70Gender-specific

Male 66/261 0.29 0.02 1.08 1.29 1.16 1.02 1.37Female 41/162 0.61 0.06 31.5 1.61 1.17 1.03 1.34

P-homogeneity between genderb 0.55 0.93Tumor size (diameter)

10 mm or less 17/65 0.36 nda 5.73 1.36 1.12 0.78 1.58.10 mm 68/268 0.43 0.08 1.74 1.43 1.16 1.05 1.31

Lymph node involvementNo lymph node involved 68/269 0.43 0.07 1.66 1.43 1.19 1.06 1.37Spread to lymph nodes 32/125 0.47 0.00 3.04 1.47 1.25 1.01 1.56

Radiation typeDose from 131I alone 107/423 0.45 0.10 1.61 1.45 1.17 1.06 1.31Dose from external exposure alone 107/423 0.38 –0.11 2.07 1.38 1.23 0.87 1.71

Model with both 131I and dose from external exposureDose from 131I, adjusted for external exposure 107/423 0.45 0.10 1.64 1.45 1.17 1.05 1.31Dose from external exposure, adjusted for 131I 107/423 0.21 –0.14 1.42 1.21 1.16 0.80 1.63

Level of dose-rate (mGy/day),10 103/415 0.34 0.10 0.86 1.34 1.15 1.07 1.2610þ 4/8 0.86 0.05 3.57 1.86 1.43 1.06 2.05

P-homogeneity between categoriesb 0.42 0.24Modeling dose uncertainties 107/423 Not available 1.20 1.07 1.43

aNot defined.bFisher’s exact test.


clean food supplied from outside the contaminatedterritories.

The overall risk estimates were compatible for 131I and forexternal exposure, and we observed the statisticallysignificant risk only for total dose and for dose from 131I.

Screening for thyroid cancer, either through formalscreening campaigns or through closer attention by medicalprofessionals has clearly occurred among Chernobylliquidators. The increased risk estimates in our study couldbe attributable to a screening related selection bias, ifscreening was, for some reason, more intensive amonggroups with higher radiation exposure from the Chernobylaccident. We have no evidence that, within the group ofliquidators, the level of screening is related to the level ofdose. All liquidators in Belarus and the Russian Federationshould undergo regular health examinations. However,physicians are not aware of the doses they received duringclean up activities. To evaluate the possible impact ofscreening, we conducted analyses by tumor size and by thefact of lymph node involvement. The majority of tumorsreviewed by the International Panel (64%) were carcinomasbigger than 10 mm in diameter, which were likely to bediagnosed even in the absence of screening. When analyseswere restricted to such tumors, risk estimates were similar tothose obtained for micro carcinomas, i.e., tumors less than10 mm. Similarly, there was little difference in risk of

tumors with and without lymph node involvement. Further,past history of thyroid diseases (which could lead toincreased screening of individuals) was not associated withincreased radiation dose [RR at 100 mGy of thyroid cancerin subjects with history of thyroid disease was 1.00 (95% CI0.89, 1.12) compared to subjects with no such history]. Thehigher proportion of the cases with older attained age in1996–2000 could be explained due to increased surveillancethat has taken place in more recent years. However, whentime since exposure and attained age were included in themodel, they did not modify the association betweenradiation dose and risk of thyroid cancer. Taken together,these results suggest that screening is unlikely to fullyexplain the increased risk in this study.

As interviews were carried out with case patients andcontrol subjects years after the Chernobyl accident, thepossibility that recall bias may have played a role in themagnitude of the increased risk estimates of thyroid cancer,observed in the present study cannot be excluded. The casepatient, aware of his/her disease status, could reportconditions of work as a liquidator, which would lead tohigher doses. It is difficult to precisely quantify the effectsof different possible recall errors. It should be noted,however, that details of work in Chernobyl reported by theliquidator were verified independently by two dosimetryexperts familiar with the clean-up practices, dates, places

TABLE 6Comparison of Risk Estimates (and 95% Confidence Intervals) with Comparable Estimates from the Atomic Bomb Survivors,

Nuclear Workers and Those Exposed to 131I in Childhood

Number of cases ERR/100 mSv 95% CI RR at 100 mSv 95% CI

External exposuresAtomic-bomb survivors (15)

Linear dose-responsea

Age at exposure,20 years 105 0.39 0.26 0.58 1.3920–40 years 87 0.10 0.03 0.19 1.10.40 years 73 0.03 ,0b 0.10 1.03Women, .20 years at exposure (40)a 241 0.07 0.02 0.15 1.07Men, .20 years at exposure (40)a 55 –0.03 ,0 0.03 0.97

15-country nuclear workers study (41)Linear ERR model 17 ,0b nda ndc

Log-linear modela 17 0.91 0.12 2.84Third follow-up of UK NRRW study (42)

54 0.32 –0.05 1.75 1.32Internal exposures

Exposure to 131I in childhood, case-control study (5)Linear ERR model up to 2 Gy 276 0.55 0.22 0.88 1.55

Swedish diagnostic 131I (43, 44)105 Not shown: no increase shown

German diagnostic 131Ib (45)13,896 0.03 0.00 0.14 1.03

Chernobyl liquidators (current study)Linear ERR model 107 0.38 0.10 1.09 1.38Log-linear model 107 1.17 1.06 1.29

a90% confidence interval for ERR/100mSv.bCentral risk estimate or lower confidence bound is on boundary of parameter space (1/max dose).cNot defined.d90% confidence interval for RR/100 mSv.


and conditions of these activities, and who were blind to thedisease status of each study subject (29). Random errors inreporting conditions of work as a liquidator could induce abias toward the null, if there was a true association betweenradiation exposure and thyroid cancer. At the same time,however, if a differential recall bias existed between casepatients and controls, this could have produced a spuriouspositive association. Analyses of individual factors thatstudy subjects may consider as being important determi-nants of radiation dose (including duration of mission,specific type of activities on the industrial site, work on theroof of the reactor) did not show any association betweenthese factors and the risk of thyroid cancer. This would beexpected if recall bias were responsible for the increasedrisk in this study. It appears unlikely that recall bias had astrong impact on the results of the present study.

Information was collected by questionnaire on a numberof different risk factors for thyroid cancer and cancer ingeneral. These included socio-economic status (measuredby education and by occupation at the time of the Chernobylaccident), other sources of radiation exposure (medical andoccupational), history of cancer or of thyroid diseases,smoking and alcohol consumption. Adjustment for thesefactors in the estimation of thyroid cancer risk did not,however, materially affect the risk estimates. These factorsare therefore unlikely to be strong confounding factors forthese diseases.

CONCLUSION

The Chernobyl accident has provided a unique opportunityto estimate the magnitude of the risk of thyroid cancer afterexposure to external radiation and to 131I. We report here resultsof a multinational case-control study of thyroid cancer riskamong Chernobyl liquidators in which considerable effortswere made to reconstruct and validate individual doseestimates. Most risk estimates were statistically significantlyelevated. They appear to be related to both 131I exposure and toexternal radiation. Risk estimates observed in our study werehigher than those estimated from most studies of otherpopulations exposed as adults. Although considerable effortswere made to reconstruct and validate individual doseestimates, uncertainties in doses and recall bias could haveaffected the magnitude of the risk estimates in this study.

The findings of our study contribute to the bettercharacterization of the risk of thyroid cancer after radiationexposure in adulthood. Further studies of populations exposedas adults, including those exposed after the Chernobylaccident, are needed to better understand this risk.

ACKNOWLEDGMENTS

This study was supported by contracts F14C-CT96-0011 and ERBIC15-

CT96-0317 from the European Union (Nuclear Fission Safety and INCO-

Copernicus Programmes) and DHSS contract no. IROI/CC/ROI5763-01 from

the U.S. National Institute for Environmental Health Sciences. The authors

would like to thank the late Professor Geoffrey Howe for helpful discussions

during the course of the study. The authors also wish to thank the interviewers

who collected the data (Belarus: Kunitski Dzmitry, Bondarovitch Pavel;

Estonia: Vello Jaakmees; Latvia: Kojalo Una; Lithuania: Stankevic Audrone;

Russia: Deniwenko Aleksandr, Frolov Gennadiy, Ganina Tatiana, Istomina

Svetlana, Shantyr Igor, Tishkovec Tatiana; the personnel of the regional

centers of the National Radiation and Epidemiological Registry in Northwest,

Volgo-Vyatsky, Central-Chernozem, North-Caucasus and Urals who

participated in the organization of the work and collection of data in the

regions; the Chernobyl Movement of Lithuania, the Latvian Association

‘‘Chernobyl’’ and the Center for Occupational Diseases and Radiation

Pathology (head physician Dr. E. Tchurbakova) at the RSU Clinical Hospital,

Latvia, for assistance in the tracing, recruitment and establishment of contact

with the study subjects; the members of the panels of pathologists and

hematologists who carried out the review of the diagnoses: Dr. Kaarle

Franssila, former Head of Oncological Pathology at the Department of

Pathology at the Helsinki University Hospital, Finland; Prof. Eugeny F.

Lushnikov and Dr. Aleksandr Abrosimov at the Medical Radiological

Research Centre, Obninsk, the Russian Federation; Dr. Yuryi D. Sidorov at the

Minsk City Bureau of Pathology, Belarus; Dr. Mikhail Fridman, at Minsk City

Oncological Dispensary, Belarus; Dr. Andre Bouville at the National Cancer

Institute, U.S., for advice on dose reconstruction issues.

Received: February 22, 2012; accepted: June 14, 2012; published online:

September 21, 2012

REFERENCES

1. Cardis E, Howe G, Ron E, Bebeshko V, Bogdanova T, Bouville A,et al. Cancer consequences of the Chernobyl accident: 20 yearsafter. J Radiol Prot 2006; 26(2):127–40.

2. UN Chernobyl Forum Expert Group ‘‘Health’’. Health Effects ofthe Chernobyl Accident and Special Health Care Programmes.Geneva: World Health Organisation; 2006.

3. UNSCEAR. Sources and Effects of Ionizing Radiation. New York:United Nations; 2011. Report No.: Volume II: Effects/ScientificAnnexes C, D and E.

4. Cardis E, Hatch M. The Chernobyl accident—an epidemiologicalperspective. Clin Oncol 2011; 23(4):251–60.

5. Cardis E, Kesminiene A, Ivanov V, Malakhova I, Shibata Y,Khrouch V, et al. Risk of thyroid cancer after exposure to 131I inchildhood. J Natl Cancer Inst 2005; 97(10):724–32.

6. Tronko MD, Howe GR, Bogdanova TI, Bouville AC, Epstein OV,Brill AB, et al. A cohort study of thyroid cancer and other thyroiddiseases after the Chornobyl accident: thyroid cancer in Ukrainedetected during first screening. J Natl Cancer Inst 2006; 98(13):897–903.

7. Astakhova LN, Anspaugh LR, Beebe GW, Bouville A, Drozdo-vitch VV, Garber V, et al. Chernobyl-related thyroid cancer inchildren of Belarus: a case-control study. Radiat Res 1998; 150(3):349–56.

8. Kopecky KJ, Stepanenko V, Rivkind N, Voilleque P, Onstad L,Shakhtarin V, et al. Childhood thyroid cancer, radiation dose fromChernobyl, and dose uncertainties in Bryansk Oblast, Russia: apopulation-based case-control study. Radiat Res 2006; 166(2):367–74.

9. Kesminiene A, Evrard AS, Ivanov VK, Malakhova IV, KurtinaitisJ, Stengrevics A, et al. Risk of hematological malignancies amongChernobyl liquidators. Radiat Res 2008; 170(6):721–35.

10. Romanenko AE, Finch SC, Hatch M, Lubin JH, Bebeshko VG,Bazyka DA, Gudzenko N, Daygil IS, Reiss RF, Bouville A, et al.The Ukrainian-American study of leukemia and related disordersamong Chornobyl cleanup workers from Ukraine: III. Radiationrisks. Radiat Res 2008; 170(6): 711–720.

11. Thompson DE, Mabuchi K, Ron E, Soda M, Tokunaga M,Ochikubo S, et al. Cancer incidence in atomic bomb survivors. PartII: Solid tumors, 1958–1987. Radiat Res 1994; 137:S17–67.


12. Preston DL, Ron E, Tokuoka S, Funamoto S, Nishi N, Soda M, etal. Solid cancer incidence in atomic bomb survivors: 1958–1998.Radiat Res 2007; 168(1):1–64.

13. Washington, DC. US NAS. Committee on the Biological Effectsof Ionizing Radiation. Health risks from exposure to low levels ofionizing radiation. BEIR: VII Report, phase II; 2006.

14. Ivanov VK, Gorski AI, Tsyb AF, Khait SE. Post-Chernobylleukemia and thyroid cancer incidence in children and adolescentsin Bryansk region: an evaluation of risks. Voprosy onkologii 2003;49(4):445–9.

15. Prisyazhniuk A, Gristchenko V, Zakordonets V, Fouzik N,Slipeniuk Y, Ryzhak I. The time trends of cancer incidence inthe most contaminated regions of the Ukraine before and after theChernobyl accident. Radiat Environ Biophys 1995; 34:3–6.

16. Fuzik M, Prysyazhnyuk A, Shibata Y, Romanenko A, FedorenkoZ, Gulak L, et al. Thyroid cancer incidence in Ukraine: trends withreference to the Chernobyl accident. Radiat Environ Biophys2011; 50(1):47–55.

17. Buzunov VN, Omelyanetz N, Strapko N, Ledoschick B,Krasnikova L, Kartushin G. Chernobyl NPP accident consequenc-es cleaning up participants in Ukraine—health status epidemio-logic study—main results. In: Brussels: European Commission;1996. P. 871–8.

18. Okeanov AE, Cardis E, Antipova SI, Polyakov SM, Sobolev AV,Bazulko NV. Health status and follow-up of liquidators in Belarus.In: Brussels: European Commission; 1996. P. 851–60.

19. Ivanov VK, Tsyb AF, Nilova EV, Efendiev VF, Gorsky AI,Pitkevich VA, et al. Cancer risks in the Kaluga oblast of theRussian Federation 10 years after the Chernobyl accident. RadiatEnviron Biophys 1997; 36(3):161–7.

20. Rahu M, Rahu K, Auvinen A, Tekkel M, Stengrevics A,Hakulinen T, et al. Cancer risk among Chernobyl cleanup workersin Estonia and Latvia, 1986–1998. Int J Cancer 2006; 119(1):162–8.

21. New York. United Nations. UNSCEAR. Sources and Effects ofIonizing Radiation - Volume II Effects; 2000.

22. Cardis E, Okeanov AE. What’s feasible and desirable in theepidemiologic follow-up of Chernobyl. In: Brussels: EuropeanCommission, editor. 1996. P. 835–50.

23. Ivanov VK, Tsyb AF, Petrov AV, Maksioutov MA, Shilyaeva TP,Kochergina EV. Thyroid cancer incidence among liquidators of theChernobyl accident. Absence of dependence of radiation risks onexternal radiation dose. Radiat Environ Biophys 2002; 41(3):195–8.

24. Chumak VV. Physical dosimetry of Chernobyl cleanup workers.Health Phys 2007; 93(5):452–61.

25. Parkin DM, Whelan SL, Ferlay J, Storm H. Cancer incidence infive continents. Vol I to VIII. Lyon: IARC Press; 2005. ReportNo.: IARC CancerBase No. 7.

26. Inskip PD, Tekkel M, Rahu M. Studies of leukemia and thyroiddisease among Chernobyl clean-up workers from the Baltics. In:National Council on Radiation Protection (NCRP) Proceeding;1997. P. 123–41.

27. Parkin DM, Whelan SL, Ferlay J, Teppo L, Thomas DB. Cancerincidence in five continents. Vol VIII. Lyon: IARC Press; 2002.Report No.: IARC Scientific Publication No. 155.

28. Ivanov VK, Tsyb AF, Maksyutov MA, Pitkevich VA, Gorsky AI,Rastopchin EM, et al. Radiation epidemiological analysis of the dataof the national Chernobyl registry of Russia: prognostication and factsnine years after the accident. Rad Prot Dos 1996; 64:121–8.

29. Kryuchkov V, Chumak V, Maceika E, Anspaugh LR, Cardis E,Bakhanova E, et al. Radrue method for reconstruction of externalphoton doses for Chernobyl liquidators in epidemiological studies.Health Phys 2009; 97(4):275–98.

30. Prohl G, Meckbach R, Muck K, Likhtarev I, Kovgan L, ChumakA, Golikov VY. Reconstruction of the doses to the population

evacuated from the 30-km zone around the Chernobyl reactor.Munich: GSF-National Researcher Center for Environment andHealth. Report No.: 07/00; 2000.

31. Gavrilin Y, Khrouch V, Shinkarev S, Drozdovitch V, Minenko V,Shemiakina E, et al. Individual thyroid dose estimation for a case-control study of Chernobyl-related thyroid cancer among childrenof Belarus-part I: 131I, short-lived radioiodines (132I, 133I, 135I),and short-lived radiotelluriums (131MTe and 132Te). Health Phys2004; 86(6):565–85.

32. Drozdovitch V, Khrouch V, Maceika E, Zvonova I, Vlasov O,Bratilova A, et al. Reconstruction of radiation doses in a case-control study of thyroid cancer following the Chernobyl accident.Health Phys 2010; 99(1):1–16.

33. Preston DL, Lubin JH, Pierce DA, McCormack VA. EPICUREUser’s Guide. Seattle, WA; 1993.

34. Preston DL, Shimizu Y, Pierce DA, Suyama A, Mabuchi K.Studies of mortality of atomic bomb survivors. Report 13: Solidcancer and noncancer disease mortality: 1950–1997. Radiat Res2003; 160(4):381–407.

35. Breslow NE, Day NE. Statistical methods in cancer research.Volume I - The analysis of case-control studies. IARC Sci Publ1980; 32:5–338.

36. Thomas D, Stram D, Dwyer J. Exposure measurement error:influence on exposure-disease. Relationships and methods ofcorrection. Annu Rev Public Health 1993; 14:69–93.

37. Stram DO, Kopecky KJ. Power and uncertainty analysis ofepidemiological studies of radiation-related disease risk in whichdose estimates are based on a complex dosimetry system: someobservations. Radiat Res 2003; 160(4):408–17.

38. Stayner L, Vrijheid M, Cardis E, Stram D, Deltour I, Gilbert S, etal. Monte Carlo maximum likelihood methods for estimatinguncertainty arising from shared errors in exposures in epidemio-logical studies. Radiat Res 2007; 168(6);757–63.

39. New York. United Nations. UNSCEAR 2006 Report. Effects ofIonizing Radiation. Report No.: Volume I Report to the GeneralAssembly/Scientific Annexes A and B; 2008.

40. Richardson DB. Exposure to ionizing radiation in adulthood andthyroid cancer incidence. Epidemiology 2009; 20(2):181–7.

41. Cardis E, Vrijheid M, Blettner M, Gilbert E, Hakama M, Hill C, etal. The 15-country collaborative study of cancer risk amongradiation workers in the nuclear industry: estimates of radiationrelated cancer risks . Radiat Res 2007; 167(4):396–416.

42. Muirhead CR, O’Hagan JA, Haylock RG, Phillipson MA,Willcock T, Berridge GL, et al. Mortality and cancer incidencefollowing occupational radiation exposure: third analysis of theNational Registry for Radiation Workers. Br J Cancer 2009;100(1):206–12.

43. Hall P, Mattsson A, Boice JD, Jr. Thyroid cancer after diagnosticadministration of iodine-131. Radiat Res 1996; 145(1):86–92.

44. Dickman PW, Holm LE, Lundell G, Boice JD, Jr., Hall P. Thyroidcancer risk after thyroid examination with 131I: a population-basedcohort study in Sweden. Int J Cancer 2003; 106(4):580–7.

45. Shore RE. Issues and epidemiological evidence regardingradiation-induced thyroid cancer. Radiat Res 1992; 131:98–111.

46. Globel B, Globel H, Andres C. Risk of hyperthyroidism afterincreasing iodine intake. Dtsch Med Wochenschr 1984; 109(27):1081–2.

47. Korobova E, Anoshko J, Kesminiene A, Kouvyline A, RomanovSA, Tenet V, et al. Evaluation of stable iodine status of the areasaffected by the Chernobyl accident in an epidemiological study inBelarus and the Russian Federation. J Geochem Explor 2010;107:124–35.

48. Armstrong BG. Effect of measurement error on epidemiologicalstudies of environmental and occupational exposures. OccupEnviron Med 1998; 55(10):651–6.


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