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American Journal of Epidemiology Advance Access originally published online on November 6, 2007
American Journal of Epidemiology 2008 167(3):305-312; doi:10.1093/aje/kwm301
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American Journal of Epidemiology © The Author 2007. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

A Cohort Study of Thyroid Cancer and Other Thyroid Diseases after the Chornobyl Accident: Dose-Response Analysis of Thyroid Follicular Adenomas Detected during First Screening in Ukraine (1998–2000)

Lydia B. Zablotska1,*, Tetyana I. Bogdanova2, Elaine Ron3, Ovsiy V. Epstein {dagger}, Jacob Robbins4, Illya A. Likhtarev5, Maureen Hatch3, Valentyn V. Markov2, Andre C. Bouville3, Valery A. Olijnyk2, Robert J. McConnell6, Victor M. Shpak2, Alina Brenner3, Galina N. Terekhova2, Ellen Greenebaum7, Valery P. Tereshchenko2, Daniel J. Fink7, Aaron B. Brill8, Galina A. Zamotayeva2, Ihor J. Masnyk3, Geoffrey R. Howe {dagger} and Mykola D. Tronko2

1 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY
2 Institute of Endocrinology and Metabolism, Kyiv, Ukraine
3 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
4 Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD
5 Scientific Center for Radiation Medicine, Academy of Medical Sciences, Kyiv, Ukraine
6 Department of Medicine, The Thyroid Clinic, College of Physicians and Surgeons, Columbia University, New York, NY
7 Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY
8 Department of Radiation and Radiological Sciences, School of Medicine, Vanderbilt University, Nashville, TN

* Correspondence to Dr. Lydia B. Zablotska, Mailman School of Public Health, Columbia University, 722 West 168th Street, Suite 1103, New York, NY 10032 (e-mail: lbz7{at}columbia.edu).

Received for publication May 17, 2007. Accepted for publication September 19, 2007.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
The Chornobyl (Chernobyl) accident in 1986 exposed many individuals to radioactive iodines, chiefly 131I, the effects of which on benign thyroid diseases are largely unknown. To investigate the risk of follicular adenoma in relation to radiation dose after Chornobyl, the authors analyzed the baseline data from a prospective screening cohort study of those exposed as children or adolescents. A stratified random sample was selected from all individuals who were younger than 18 years, had thyroid radioactivity measurements taken within 2 months after the accident, and resided in the three heavily contaminated areas in Ukraine. This analysis is based on the 23 cases diagnosed in 12,504 subjects for whom personal history of thyroid diseases was known. The dose-response relation was linear with an excess relative risk of 2.07 per gray (95% confidence interval: 0.28, 10.31). The risk was significantly higher in women compared with men, with no clear modifying effects of age at exposure. In conclusion, persons exposed to radioactive iodines as children and adolescents have an increased risk of follicular adenoma, though it is smaller than the risk of thyroid cancer in the same cohort. Compared with results from other studies, this estimate is somewhat smaller, but confidence intervals overlap, suggesting compatibility.

adenoma; Chernobyl nuclear accident; dose-response relationship, radiation; iodine; thyroid neoplasms

Abbreviations: CI, confidence interval


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
The accident at the Chornobyl (Chernobyl) nuclear power plant in Ukraine in April 1986 resulted in the release into the atmosphere of large amounts of radionuclides (chiefly 131I, with contributions from 133I and 133Cs) (1). The radioactive iodines accumulated in the human thyroid gland via the consumption of 131I-contaminated milk and other food items. Previous studies have shown that the populations of Ukraine, Belarus, and the Russian Federation have experienced a large increase of thyroid cancer in those exposed to the fallout before the age of 18 years (2–7). This increase became apparent 4–5 years after the accident and confirmed previous suggestions that thyroid cancer is one of the most radiosensitive tumors when exposure occurs at young ages (8).

Various studies of external irradiation have suggested that, along with thyroid cancer, thyroid follicular adenoma is a sensitive outcome for detecting the effects of childhood exposure to external ionizing radiation (9–19). However, the study of benign thyroid tumors has been hampered by lack of data on baseline risks and limitations of passive data collection on noncancer outcomes (20).

Studies of diagnostic and therapeutic doses of 131I have mostly evaluated thyroid cancer (21–25). An exception is the study by Hall et al. (26) that showed a significant dose-response relation between diagnostic administration of 131I and thyroid nodularity among women. The results of the studies investigating the effects of exposures to environmental radioactive iodines on benign thyroid tumors have been contradictory, ranging from no effect (27) to an effect comparable in magnitude with that for external irradiation (28, 29).

The Chornobyl accident presents an unparalleled opportunity to study the association between radioactive iodines and a spectrum of thyroid diseases. While there have been several analytical epidemiologic studies of thyroid cancer following the Chornobyl accident (4–6), none has evaluated follicular adenoma. In this paper, we present risk estimates of follicular adenoma in relation to individual 131I thyroid doses and discuss the effects of gender, age at exposure, iodine deficiency, and other possible effect-modifying factors.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
A detailed description of the study methods has been published previously (30). In brief, we made use of a database of thyroid radioactivity measurements taken in individuals younger than 18 years residing in the three most contaminated oblasts in Ukraine within 2 months after the Chornobyl accident; an oblast is an administrative area similar in size to a state or province.

The cohort
A stratified random sample of 32,385 persons was selected from this database and included all individuals with measured thyroid activity doses of ≥1 gray (Gy) and a random sample from two lower-dose groups (0–0.29 and 0.30–0.99 Gy). Various methods were used to trace these subjects and to invite them for screening (n = 19,612). Between 1998 and 2000, 13,243 (67.5 percent of those invited, 40.9 percent of selected sample) subjects were recruited into the study and screened for thyroid diseases. A total of 118 (0.9 percent) subjects were excluded from the analyses because of inadequate dose estimates (n = 26), out-of-range date of birth (n = 31), history of thyroid cancer prior to screening (n = 14), history of thyroid surgery for benign pathology (n = 21), and incomplete examinations (n = 26); none was diagnosed with follicular adenoma by the end of the third screening cycle. Those with missing information on self-reported history of thyroid diseases, an important a priori confounder (9, 12) (n = 621), were excluded from further analyses, leaving 12,504 subjects for current analysis. Excluding those with missing information did not materially change our results.

Screening procedures
All subjects received an ultrasonographic examination and palpation of the thyroid gland by a sonographer, as well as an independent clinical examination including palpation by an endocrinologist (30). Any discrepancies between palpation results were resolved by a third examination conducted jointly by both doctors. The screening examination also included taking a blood sample for estimating thyroid hormones and antibodies, taking a spot urine sample to estimate current iodine excretion (31), and conducting a series of structured questionnaires on personal and family medical history and on residential and dietary histories relevant to radiation dose estimation (32).

Fine-needle aspiration biopsy
Thyroid nodules or focal lesions with the largest diameter >10 mm or smaller nodules 5–10 mm in size, at least partially solid and with indirect signs of malignancy, detected by either palpation or ultrasonography were referred for fine-needle aspiration biopsy under ultrasound guidance (30, p. 487). Of the 345 subjects referred for fine-needle biopsy, the referral was deemed unnecessary after repeated ultrasound for 61 subjects. By the end of 2001, fine-needle aspiration biopsy was performed for 92.6 percent of the remaining subjects; biopsy compliance did not differ by dose (p = 0.47).

Dosimetry
The information from the questionnaires was combined with individual 131I thyroid activity measurements and models of environmental transfer and metabolism of radioiodines to estimate individual thyroid doses (32). To account for uncertainties in the results of the thyroid activity measurements, as well as in the values of the environmental and metabolic parameters involved in the estimation of the thyroid doses, 1,000 dose calculations were performed with a Monte Carlo procedure for each subject (32, 33). All analyses are based on the individual arithmetic means of the 1,000 dose simulations. Only intakes of 131I were considered in the estimation of the thyroid doses, as it has been shown in a case-control study in Belarus that this pathway of exposure represented, on average, about 95 percent of the thyroid dose (34, 35). Other contributions included short-lived (mainly 133I and 132Te) and long-lived (mainly 134Cs and 137Cs) radionuclides and external exposure from radionuclides deposited on the ground and on building materials. Plans have been made to estimate their contribution to the thyroid dose for all cohort subjects in Ukraine, but there is no reason to expect that the average contribution from these pathways will differ substantially from the results in Belarus (30).

Thyroid doses in this cohort ranged from 0 to 48 Gy with an arithmetic mean of 0.77 Gy (standard deviation: 1.85). Sixty-seven percent of the cohort had doses below 0.5 Gy and 43 percent below 0.2 Gy.

Statistical methods
The principal method of analysis was based on comparing the prevalence of follicular adenoma in the cohort across the dose range using logistic regression modeling for Bernoulli data (36). The categorical analysis of the data was based on four dose categories, the cutpoints for which were chosen to evenly distribute all cases. The excess relative risk model was applied to continuous doses to estimate the excess relative risk per gray and to evaluate the shape of the dose response:

Formula
where {lambda}, {delta}, and {varepsilon} are functions of the background risks, the dose-related risks, and the risk-modifying factors, respectively; z is possible background (z0) or risk-modifying (ze) factors; and β is dose parameters to be estimated from either a linear or quadratic function of dose (βdose) or from a cell sterilization term (βe). Thus, any risk associated with radiation exposure multiplies the background risk from independent risk factors, such as gender, age at exposure, current iodine status, and personal and family history of thyroid diseases and cancers in general. We also evaluated an alternative model for estimation of an excess absolute risk of radiation exposure:

Formula

Because Chornobyl exposure happened over a short period of time (and subjects were screened over a 2-year period), the age at exposure correlates with the age at screening almost perfectly (Pearson's r = 0.99). We used the age at screening to adjust the background rates, because the age at screening is applicable whether or not an individual has been exposed to radiation. However, when we evaluated the modifying effects of age on the risk of follicular adenoma from radiation dose, the age at exposure was used because it is a biologically relevant measure.

All analyses were performed by use of the GMBO module of the EPICURE computer software package (37). When variables were evaluated as possible background factors, dose parameter was retained in the model to control for the main effects of dose and for possible confounding between the dose effect and the background risk factor. Variables were retained in the model if they significantly improved the fit of the model, as evaluated by the likelihood ratio test comparing the deviances from the two nested models, or if they changed the risk estimate by more than 10 percent. All statistical tests were two sided with a specified type I error of 0.05, and 95 percent confidence intervals were estimated by maximum likelihood procedures.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
Study subjects
All 12,504 study participants were screened in May 1998–December 2000. Cases of follicular adenoma were defined as subjects referred for fine-needle aspiration biopsy because of abnormal findings on palpation and/or ultrasound examination during screening, followed by referral to surgery and subsequent pathomorphologic diagnosis of follicular adenoma by study pathologists. All subjects referred for surgery complied, and all diagnoses were confirmed by the International Pathology Panel of thyroid experts established in the framework of the Chornobyl Tissue Bank Project (38), resulting in 23 confirmed cases of follicular adenoma.

One of the 23 cases was diagnosed with papillary thyroid cancer during surgery for follicular adenoma. Both lesions were located in the same lobe, but in nonadjacent areas. Exclusion of this case from analysis did not change the results, and the case was retained in all subsequent analyses.

The majority of the cases were female (n = 16, 70 percent). Age at diagnosis did not differ significantly between males and females, with an average age at diagnosis of 24.7 (standard deviation: 4.3) years.

Effects of nonradiation risk factors
Table 1 shows that, after adjustment for dose and other confounders, women had a two times higher risk of follicular adenoma compared with men (odds ratio = 1.87, 95 percent confidence interval (CI): 0.76, 5.04). Older age at the time of screening was significantly associated with increased risk, with subjects aged 25–33 years almost four times more likely to develop follicular adenoma compared with those aged 12–20 years (p = 0.03). A trend test showed a monotonic increase in risk with age at screening (p = 0.01).


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  		TABLE 1. Odds ratios and 95 percent confidence intervals of follicular adenoma for selected background risk factors, Ukraine, 1998–2000

 
A personal history of thyroid disease had a significant effect on the subsequent development of follicular adenoma. With adjustment for dose and other confounders, subjects reporting a history of thyroid diseases were almost six times more likely to develop follicular adenoma (odds ratio = 5.62, 95 percent CI: 2.18, 13.60) than those without such a history. Subjects residing in Kyiv City and the Chernihiv oblast had a three times higher risk of developing follicular adenoma compared with subjects from the Zhytomyr or Kyiv oblasts. Marital status at the time of screening, urban/rural current residence, a history of thyroid diseases in first-degree relatives, and current iodine excretion did not influence the risk of follicular adenoma (table 1).

Effects of thyroid dose
Table 2 shows that, in the categorical dose-response analysis, odds ratios increased monotonically, with the risk of follicular adenoma in the highest category being almost six times higher than that in the lowest category. Odds ratios were heterogeneous across dose categories and exhibited a strong linear trend (phomogeneity = 0.01, ptrend < 0.01) (figure 1).


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  		TABLE 2. Odds ratios and 95 percent confidence intervals of follicular adenoma by thyroid dose category, Ukraine, 1998–2000

 

Figure 1
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  		FIGURE 1. Plot of the log odds ratio with the corresponding 95% confidence intervals of follicular adenoma by mean dose for each of four dose categories and a fitted dose-response curve constructed using the least-squares method, Ukraine, 1998–2000.

 
Table 3 presents the results of fitting the excess relative risk model to the data. After adjustment for confounders, those exposed to a thyroid dose of 1 Gy had three times the risk of follicular adenoma compared with those with zero dose, an excess relative risk of 2.07 per gray (95 percent CI: 0.28, 10.31; p < 0.01). The dose response was linear, and addition of a quadratic term in dose did not improve the fit (p = 0.76), indicating that there was no quadratic curvature. Addition of a log-linear excess relative risk term to the model with the linear term in dose also did not improve the fit of the model (coefficient = –0.11; p = 0.30). The presence of the negative downturn completely depended on the presence of subjects with extremely high doses and disappeared when the upper limit of the dose range was truncated at 8 Gy. With adjustment for background confounders, the estimated excess relative risk for those with doses below 8 Gy was 2.54 per gray (95 percent CI: 0.45, 12.17).


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  		TABLE 3. Models of excess relative risk per gray and interactions of dose, gender, history of thyroid diseases, and categories of iodine excretion, Ukraine, 1998–2000

 
Using an alternative model assuming that radiation-related and background risks of follicular adenoma are additive, we estimated an excess absolute risk of adenoma at 4.03 (95 percent CI: 0, 15.45) cases per 10,000 person-years x per gray (not shown).

Effects of modifying factors on the dose response
Table 3 presents the results of analyses investigating the influences of various dose-effect–modifying factors. We observed a statistically significant difference in the effect of dose in males and females, but there were only seven male cases, and the confidence interval was very wide.

In our analysis, the age at exposure was not an effect modifier, and there was no evidence that younger age at exposure increased the subsequent risk of follicular adenoma. We did not observe a modifying effect of iodine deficiency as measured by the history of thyroid diseases or by either current iodine excretion (table 3) or oblast of residence (not shown). We also did not find a modifying effect of family history of thyroid diseases (p = 0.43) or family history of any type of cancer (none for cases, not shown).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
This paper reports the results of the first epidemiologic study of the association between radiation exposure from radioactive iodine fallout from the Chornobyl accident and subsequent risk of follicular adenoma in those exposed when younger than 18 years. The data exhibited a strong positive linear dose-response relation between 131I thyroid dose and follicular adenoma, with an estimated excess relative risk of 2.07 per gray (95 percent CI: 0.28, 10.31). Women had a significantly higher risk compared with men, although the number of cases in males was small, and the confidence interval was wide. Age-at-exposure effects were not clear, and no consistent pattern emerged.

Among the major strengths of the study are the availability of individual 131I thyroid doses based on thyroid radioactivity measurements made within 2 months after the accident and questionnaire data collected during screening. Our findings are further strengthened by the high fine-needle biopsy compliance rate of 93 percent. Because all those referred for surgery following fine-needle aspiration biopsy have been operated upon, it is unlikely that follicular adenoma was underdiagnosed.

Caution should be exercised in interpreting the findings of this study as they are based on a small number of cases and, therefore, have limited power. The study also has some other limitations: 1) only 40.9 percent of those selected from the file of thyroid activity measurements or 67.5 percent of those invited to participate were screened; 2) uncertainties in dosimetry have not been taken into account; and 3) prevalence odds ratios were used to approximate relative risks. Participants (n = 13,243) and nonparticipants (n = 19,142) had similar distributions of gender but significantly different distributions of oblast of residence, which was primarily the result of higher mobility and associated difficulties in tracing subjects from the Zhytomyr and Kyiv oblasts. Participation rates were significantly lower for those older at the time of the accident as they were more likely to move away from the screening area by 1998–2000. Because the distributions of measured thyroid activity were similar among participants and nonparticipants, it appears unlikely that nonparticipation could have introduced any meaningful bias. In addition, our analyses were adjusted for possible confounders and effect modifiers to avoid any potential effects of differential distribution of such variables among participants and nonparticipants.

With regard to the second limitation, we believe that the majority of uncertainties in dosimetry were the result of random error, and thus their potential effects would most likely be to attenuate risk estimates. The major sources of uncertainty were related to the thyroid mass and to the content of 131I in the thyroid gland in 1986. Other sources included transfer of 131I in the environment, reduction in its concentrations in foodstuffs between production and consumption, its metabolism in the human body, and questionnaire data. The uncertainties in the estimates of the individual thyroid doses were found to be approximately lognormally distributed, with geometric standard deviations ranging from 1.6 to 5.0 and median = 1.7. These uncertainties are comparable to, and in most cases smaller than, those reported for studies of environmental 131I (27, 29, 39, 40).

Finally, we believe that screening-detected thyroid adenomas progress to clinically detected adenomas, and therefore the prevalence odds ratio should be a good approximation of the relative risk.

Several risk factors were examined as possible effect modifiers of the dose-dependent risk of follicular adenoma. In contrast with a study of external radiation exposure (9), neither family history of thyroid cancer or other thyroid diseases nor family history of any type of cancer interacted with radiation dose.

Previous studies (8, 10, 41) reported that individuals exposed to external ionizing irradiation at the ages of 0–5 years had a higher risk of developing thyroid cancer compared with those exposed at a later age. Recently, we showed that the highest risk for thyroid cancer among those exposed to radioactive iodines was for the youngest age group (0–5 years) (6). Studies of benign neoplasia after irradiation showed contradictory evidence, with some studies exhibiting no effects of age at exposure (13, 19) and others a strong inverse effect (10, 12). We estimated the highest excess relative risk for follicular adenoma for those exposed at 5–10 years (excess relative risk = 3.34 per gray), although risk estimates for three age categories were not significantly different (p = 0.60). To compare our results with those of other studies, we examined effect modification by age at exposure for the combined outcome "thyroid neoplasia," a category which combines follicular adenoma with thyroid cancer. The highest risk was observed in the age group 5–10 years, but it was not significantly different from the risk estimates in other age-at-exposure groups (p = 0.72). Similar age-at-exposure effects were observed in a large screening survey of 86,000 individuals from Belarus, Ukraine, and the Russian Federation exposed to radioactive fallout, the Chernobyl Sasakawa Health and Medical Cooperation Project, which reported age at exposure of 5–6 years as a separating threshold for significant disease prevalence, with thyroid cancer increased before the threshold and benign thyroid lesions after the threshold (42, p. 118).

We also examined interaction between dose and several proxy indicators of iodine deficiency, such as history of thyroid diseases, place of residence, and current iodine excretion, but found no evidence of effect modification. The oblast of residence is of particular interest because, in the wake of the Chornobyl accident, those living within the 30-km zone were relocated to other areas of Ukraine, mostly within the same oblasts. Thus, oblast of current residence coincides with the oblast of residence at the time of the accident in 1986 and is a proxy for endemic iodine deficiency.

Our estimates of risk were somewhat lower than those reported from the cohort studies of external irradiation, which reported risks of 6–10 per gray (9, 10, 12). However, our study has a much younger population with shorter follow-up, and several of the other studies have shown that latency for benign tumors is longer than that for thyroid cancer.

The excess relative risk of follicular adenoma in our analysis was lower than the risk of thyroid cancer published previously (2.07 vs. 5.25 per gray) (6). The excess absolute risk of adenoma was also smaller (4.03 vs. 28.75 cases/10,000 person-years per gray). However, most of the cancers in this cohort were of the papillary type, and thus it was not possible to compare radiation-related risks for follicular adenoma and follicular cancer, which generally occurs at older ages. Further follow-up is needed to clarify these issues.

Three retrospective cohort studies have evaluated the effects of environmental exposures to radioactive iodines. Hamilton et al. (28) investigated the effects of iodine from nuclear fallout in Marshall Islanders. However, no thyroid doses were available for analysis. The other two, one investigating the effects of the fallout after nuclear weapons testing at the Nevada test site (29) and the other (the Hanford Thyroid Disease Study) (27) investigating the effects of atmospheric releases, relied on dose reconstructions based on residential history years after exposures had occurred, and they were based on small numbers of cases of "thyroid neoplasia."

Our risk estimate for "thyroid neoplasia" was 4.39 per gray (95 percent CI: 1.67, 13.28; n = 58 cases). This is lower than an excess relative risk of 13.0 per gray (95 percent CI: 2.7, 68.7; n = 20) from the Nevada test site study (29) and much higher than 0.1 per gray (95 percent CI: <–0.3, 2.2; n = 33) from the Hanford Thyroid Disease Study (27). Davis et al. (27) have suggested that some of the differences in estimates lie in the different composition of the radionuclides in the fallout: While the Hanford Thyroid Disease Study thyroid dose was mostly due to 131I, other radionuclides as well as external ionizing radiation exposures had greater contribution in the doses analyzed in the Nevada test site study. Hoffman et al. (43) suggested that high uncertainties in dose reconstructions in the Hanford Thyroid Disease Study may account for negative findings. Because in our cohort 131I accounted for about 95 percent of the thyroid dose, our estimate should be closer to the lower of the two risk estimates (30, 32).

In summary, our findings indicate that follicular adenoma is strongly related to exposure from radioactive iodines. The shape of the dose response is linear. Radiation-related risks are modified by gender with the effect significantly larger in females. Age at exposure, history of thyroid diseases, oblast of residence, and current iodine excretion do not modify the risk of follicular adenoma. Our risk estimates were smaller compared with those of studies of follicular adenoma following exposures to external ionizing radiation, but the confidence intervals overlap, suggesting that the tumorigenic effects of radioactive iodines and external irradiation among those exposed as children and adolescents are comparable. The risk of follicular adenoma in our analysis was lower than the risk of thyroid cancer observed in the same cohort published previously.


   ACKNOWLEDGMENTS
 
The study team acknowledges the Louise Hamilton Kyiv Data Management Center of the University of Illinois at Chicago, supported in part by the US National Institutes of Health Fogarty International Center, and its head Oleksandr Zvinchuk, for excellent assistance with cohort database support and data management. The authors gratefully acknowledge the confirmation of diagnosis provided by the International Pathology Panel of the Chornobyl Tissue Bank: Dr. A. Abrosimov and Professors T. Bogdanova, M. Ito, V. LiVolsi, J. Rosai, and E. D. Williams.

This article is dedicated to the memory of Dr. Geoffrey R. Howe, without whose unswerving dedication and hard work over many years this study would not have been possible.

Conflict of interest: none declared.


   NOTES
 
{dagger} Deceased. Back


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). 2000 report to the General Assembly, with scientific annexes. Vol II. Effects. (2000) New York, NY: United Nations.
  2. Jacob P, Kenigsberg Y, Zvonova I, et al. Childhood exposure due to the Chernobyl accident and thyroid cancer risk in contaminated areas of Belarus and Russia. Br J Cancer (1999) 80:1461–9.[CrossRef][Web of Science][Medline]
  3. Likhtarev IA, Sobolev BG, Kairo IA, et al. Thyroid cancer in the Ukraine. (Letter). Nature (1995) 375:365.[Medline]
  4. Davis S, Stepanenko V, Rivkind N, et al. Risk of thyroid cancer in the Bryansk Oblast of the Russian Federation after the Chernobyl Power Station accident. Radiat Res (2004) 162:241–8.[CrossRef][Web of Science][Medline]
  5. Cardis E, Kesminiene A, Ivanov V, et al. Risk of thyroid cancer after exposure to 131I in childhood. J Natl Cancer Inst (2005) 97:724–32.[Abstract/Free Full Text]
  6. Tronko MD, Howe GR, Bogdanova TI, et al. A cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: thyroid cancer in Ukraine detected during first screening. J Natl Cancer Inst (2006) 98:897–903.[Abstract/Free Full Text]
  7. Jacob P, Bogdanova TI, Buglova E, et al. Thyroid cancer risk in areas of Ukraine and Belarus affected by the Chernobyl accident. Radiat Res (2006) 165:1–8.[CrossRef][Web of Science][Medline]
  8. Ron E, Lubin JH, Shore RE, et al. Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. Radiat Res (1995) 141:259–77.[Web of Science][Medline]
  9. Shore RE, Hildreth N, Dvoretsky P, et al. Benign thyroid adenomas among persons x-irradiated in infancy for enlarged thymus glands. Radiat Res (1993) 134:217–23.[CrossRef][Web of Science][Medline]
  10. Ron E, Modan B, Preston D, et al. Thyroid neoplasia following low-dose radiation in childhood. Radiat Res (1989) 120:516–31.[Web of Science][Medline]
  11. Nagataki S, Shibata Y, Inoue S, et al. Thyroid diseases among atomic bomb survivors in Nagasaki. JAMA (1994) 272:364–70.[Abstract/Free Full Text]
  12. Imaizumi M, Usa T, Tominaga T, et al. Radiation dose-response relationships for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki atomic bomb survivors 55–58 years after radiation exposure. JAMA (2006) 295:1011–22.[Abstract/Free Full Text]
  13. Shore RE, Moseson M, Harley N, et al. Tumors and other diseases following childhood x-ray treatment for ringworm of the scalp (Tinea capitis). Health Phys (2003) 85:404–8.[CrossRef][Web of Science][Medline]
  14. Janower ML, Miettinen OS. Neoplasms after childhood irradiation of the thymus gland. JAMA (1971) 215:753–6.[Abstract/Free Full Text]
  15. Acharya S, Sarafoglou K, LaQuaglia M, et al. Thyroid neoplasms after therapeutic radiation for malignancies during childhood or adolescence. Cancer (2003) 97:2397–403.[CrossRef][Web of Science][Medline]
  16. Pottern LM, Kaplan MM, Larsen PR, et al. Thyroid nodularity after childhood irradiation for lymphoid hyperplasia: a comparison of questionnaire and clinical findings. J Clin Epidemiol (1990) 43:449–60.[CrossRef][Web of Science][Medline]
  17. Fleming ID, Black TL, Thompson EI, et al. Thyroid dysfunction and neoplasia in children receiving neck irradiation for cancer. Cancer (1985) 55:1190–4.[CrossRef][Web of Science][Medline]
  18. Hancock SL, McDougall IR, Constine LS. Thyroid abnormalities after therapeutic external radiation. Int J Radiat Oncol Biol Phys (1995) 31:1165–70.[CrossRef][Web of Science][Medline]
  19. Schneider AB, Ron E, Lubin J, et al. Dose-response relationships for radiation-induced thyroid cancer and thyroid nodules: evidence for the prolonged effects of radiation on the thyroid. J Clin Endocrinol Metab (1993) 77:362–9.[Abstract]
  20. Gilbert ES, Land CE, Simon SL. Health effects from fallout. Health Phys (2002) 82:726–35.[CrossRef][Web of Science][Medline]
  21. Holm LE, Hall P, Wiklund K, et al. Cancer risk after iodine-131 therapy for hyperthyroidism. J Natl Cancer Inst (1991) 83:1072–7.[Abstract/Free Full Text]
  22. Ron E, Doody MM, Becker DV, et al. Cancer mortality following treatment for adult hyperthyroidism. Cooperative Thyrotoxicosis Therapy Follow-up Study Group. JAMA (1998) 280:347–55.[Abstract/Free Full Text]
  23. Franklyn JA, Maisonneuve P, Sheppard M, et al. Cancer incidence and mortality after radioiodine treatment for hyperthyroidism: a population-based cohort study. Lancet (1999) 353:2111–15.[CrossRef][Web of Science][Medline]
  24. Hahn K, Schnell-Inderst P, Grosche B, et al. Thyroid cancer after diagnostic administration of iodine-131 in childhood. Radiat Res (2001) 156:61–70.[CrossRef][Web of Science][Medline]
  25. Dickman PW, Holm LE, Lundell G, et al. Thyroid cancer risk after thyroid examination with 131I: a population-based cohort study in Sweden. Int J Cancer (2003) 106:580–7.[CrossRef][Web of Science][Medline]
  26. Hall P, Furst CJ, Mattsson A, et al. Thyroid nodularity after diagnostic administration of iodine-131. Radiat Res (1996) 146:673–82.[CrossRef][Web of Science][Medline]
  27. Davis S, Kopecky KJ, Hamilton TE, et al. Thyroid neoplasia, autoimmune thyroiditis, and hypothyroidism in persons exposed to iodine 131 from the Hanford nuclear site. JAMA (2004) 292:2600–13.[Abstract/Free Full Text]
  28. Hamilton TE, van Belle G, LoGerfo JP. Thyroid neoplasia in Marshall Islanders exposed to nuclear fallout. JAMA (1987) 258:629–35.[Abstract/Free Full Text]
  29. Lyon JL, Alder SC, Stone MB, et al. Thyroid disease associated with exposure to the Nevada nuclear weapons test site radiation: a reevaluation based on corrected dosimetry and examination data. Epidemiology (2006) 17:604–14.[CrossRef][Web of Science][Medline]
  30. Stezhko VA, Buglova EE, Danilova LI, et al. A cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: objectives, design and methods. Radiat Res (2004) 161:481–92.[CrossRef][Web of Science][Medline]
  31. Tronko ND, Kravchenko VI, Fink DJ, et al. Iodine excretion in regions of Ukraine affected by the Chornobyl accident: experience of the Ukrainian-American cohort study of thyroid cancer and other thyroid diseases. Thyroid (2005) 15:71–7.
  32. Likhtarev I, Bouville A, Kovgan L, et al. Questionnaire- and measurement-based individual thyroid doses in Ukraine resulting from the Chornobyl nuclear reactor accident. Radiat Res (2006) 166:271–86.[CrossRef][Web of Science][Medline]
  33. Likhtarev I, Minenko V, Khrouch V, et al. Uncertainties in thyroid dose reconstruction after Chernobyl. Radiat Prot Dosimetry (2003) 105:601–8.[Abstract]
  34. Minenko VF, Ulanovsky AV, Drozdovitch VV, et al. Individual thyroid dose estimates for a case-control study of Chernobyl-related thyroid cancer among children of Belarus—part II. Contributions from long-lived radionuclides and external radiation. Health Phys (2006) 90:312–27.[CrossRef][Web of Science][Medline]
  35. Gavrilin Y, Khrouch V, Shinkarev S, et al. Individual thyroid dose estimation for a case-control study of Chernobyl-related thyroid cancer among children of Belarus—part I. 131I, short-lived radioiodines (132I, 133I, 135I), and short-lived radiotelluriums (131mTe and 132Te). Health Phys (2004) 86:565–85.[CrossRef][Web of Science][Medline]
  36. Breslow NE, Day NE. Statistical methods in cancer research. Vol II. The design and analysis of cohort studies. (1987) Lyon, France: International Agency for Research on Cancer. (IARC scientific publication no. 82).
  37. Preston DL, Lubin JH, Pierce DA, et al. EPICURE user's guide. (1993) Seattle, WA: Hirosoft International Corporation.
  38. Thomas GA, Williams ED. Thyroid tumor banks. (Letter). Science (2000) 289:2283.[Medline]
  39. Stepanenko VF, Voilleque PG, Gavrilin YI, et al. Estimating individual thyroid doses for a case-control study of childhood thyroid cancer in Bryansk Oblast, Russia. Radiat Prot Dosimetry (2004) 108:143–60.[Abstract/Free Full Text]
  40. Drozdovitch V, Maceika E, Khrouch V, et al. Uncertainties in individual doses in a case control study of thyroid cancer after the Chernobyl accident. Radiat Prot Dosimetry (DOI:10.1093/rpd/ncm360).
  41. Thompson DE, Mabuchi K, Ron E, et al. Cancer incidence in atomic bomb survivors. Part II: solid tumors, 1958 –1987. Radiat Res (1994) 137(suppl):S17–67.[Web of Science][Medline]
  42. Ito M, Yamashita S, Ashizawa K, et al. Pediatric thyroid diseases around Chernobyl: morphological aspects of the Chernobyl Sasakawa Health and Medical Cooperation Project. In: Chernobyl: a decade—Yamashita S, Shibata Y, eds. (1997) Amsterdam, Netherlands: Elsevier Science BV.
  43. Hoffman FO, Ruttenber AJ, Greenland S, et al. Radiation exposure and thyroid cancer. (Letter). JAMA (2006) 296. 513; author reply 514.

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