Impact of Uncertainties in Exposure Assessment on Thyroid Cancer Risk among Persons in Belarus Exposed as Children or Adolescents Due to the Chernobyl Accident.

The excess incidence of thyroid cancer in Ukraine and Belarus observed a few years after the Chernobyl accident is considered to be largely the result of 131I released from the reactor. Although the Belarus thyroid cancer prevalence data has been previously analyzed, no account was taken of dose measurement error.We examined dose-response patterns in a thyroid screening prevalence cohort of 11,732 persons aged under 18 at the time of the accident, diagnosed during 1996-2004, who had direct thyroid 131I activity measurement, and were resident in the most radio-actively contaminated regions of Belarus. Three methods of dose-error correction (regression calibration, Monte Carlo maximum likelihood, Bayesian Markov Chain Monte Carlo) were applied.There was a statistically significant (p<0.001) increasing dose-response for prevalent thyroid cancer, irrespective of regression-adjustment method used. Without adjustment for dose errors the excess odds ratio was 1.51 Gy- (95% CI 0.53, 3.86), which was reduced by 13% when regression-calibration adjustment was used, 1.31 Gy- (95% CI 0.47, 3.31). A Monte Carlo maximum likelihood method yielded an excess odds ratio of 1.48 Gy- (95% CI 0.53, 3.87), about 2% lower than the unadjusted analysis. The Bayesian method yielded a maximum posterior excess odds ratio of 1.16 Gy- (95% BCI 0.20, 4.32), 23% lower than the unadjusted analysis. There were borderline significant (p = 0.053-0.078) indications of downward curvature in the dose response, depending on the adjustment methods used. There were also borderline significant (p = 0.102) modifying effects of gender on the radiation dose trend, but no significant modifying effects of age at time of accident, or age at screening as modifiers of dose response (p>0.2).In summary, the relatively small contribution of unshared classical dose error in the current study results in comparatively modest effects on the regression parameters

Parameter estimates and 95% profile likelihood-based confidence intervals (95% CI) (or 95% Bayesian credible intervals (BCI)) for analysis of curvature in fits of excess odds ratio model (1) with or without adjustment for dose errors using regression calibration, for various sets of doses.

<p>^aunless otherwise stated all <i>p</i>-values refer to the improvement in fit of the current row in the Table with that of the model fitted in the row immediately above.</p><p>^b<i>p</i>-value of improvement in fit compared with a model with linear-exponential dose terms.</p><p>^c<i>p</i>-value of improvement in fit compared with a model with no dose terms.</p><p>^ddeviance information criterion [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139826#pone.0139826.ref024" target="_blank">24</a>].</p><p>^eposterior distribution maximum probability estimate.</p><p>^f95% Bayesian credibility interval (BCI).</p><p>All models have underlying rates adjusted for age (treated categorically), gender and oblast.</p

Dose-response (+95 CI) for thyroid cancer in relation to deterministic [4, 21], and regression-calibration adjusted doses (arithmetic means of 1,000 individual stochastic doses) [22].

<p>The models are adjusted for age (treated categorically), gender and oblast in the baseline. Dashed red line shows odds ratio = 1. The lower panel shows the lower dose (<0.5 Gy) part of the dose response.</p

Variation of excess relative risk with age at the time of the accident (using regression calibration adjusted doses).

<p>Other details as for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139826#pone.0139826.g001" target="_blank">Fig 1</a>.</p

Risk of thyroid follicular adenoma among children and adolescents in Belarus exposed to iodine-131 after the Chornobyl accident.

Several studies reported an increased risk of thyroid cancer in children and adolescents exposed to radioactive iodines, chiefly iodine-131 ((131)I), after the 1986 Chornobyl (Ukrainian spelling) nuclear power plant accident. The risk of benign thyroid tumors following such radiation exposure is much less well known. We have previously reported a novel finding of significantly increased risk of thyroid follicular adenoma in a screening study of children and adolescents exposed to the Chornobyl fallout in Ukraine. To verify this finding, we analyzed baseline screening data from a cohort of 11,613 individuals aged ≤18 years at the time of the accident in Belarus (mean age at screening = 21 years). All participants had individual (131)I doses estimated from thyroid radioactivity measurements and were screened according to a standardized protocol. We found a significant linear dose response for 38 pathologically confirmed follicular adenoma cases. The excess odds ratio per gray of 2.22 (95% confidence interval: 0.41, 13.1) was similar in males and females but decreased significantly with increasing age at exposure (P &lt; 0.01), with the highest radiation risks estimated for those exposed at &lt;2 years of age. Follicular adenoma radiation risks were not significantly modified by most indicators of past and current iodine deficiency. The present study confirms the (131)I-associated increases in risk of follicular adenoma in the Ukrainian population and adds new evidence on the risk increasing with decreasing age at exposure

Risk of thyroid follicular adenoma among children and adolescents in Belarus exposed to iodine-131 after the Chornobyl accident.

Several studies reported an increased risk of thyroid cancer in children and adolescents exposed to radioactive iodines, chiefly iodine-131 ((131)I), after the 1986 Chornobyl (Ukrainian spelling) nuclear power plant accident. The risk of benign thyroid tumors following such radiation exposure is much less well known. We have previously reported a novel finding of significantly increased risk of thyroid follicular adenoma in a screening study of children and adolescents exposed to the Chornobyl fallout in Ukraine. To verify this finding, we analyzed baseline screening data from a cohort of 11,613 individuals aged ≤18 years at the time of the accident in Belarus (mean age at screening = 21 years). All participants had individual (131)I doses estimated from thyroid radioactivity measurements and were screened according to a standardized protocol. We found a significant linear dose response for 38 pathologically confirmed follicular adenoma cases. The excess odds ratio per gray of 2.22 (95% confidence interval: 0.41, 13.1) was similar in males and females but decreased significantly with increasing age at exposure (P &lt; 0.01), with the highest radiation risks estimated for those exposed at &lt;2 years of age. Follicular adenoma radiation risks were not significantly modified by most indicators of past and current iodine deficiency. The present study confirms the (131)I-associated increases in risk of follicular adenoma in the Ukrainian population and adds new evidence on the risk increasing with decreasing age at exposure

Analysis of thyroid malignant pathologic findings identified during 3 rounds of screening (1997-2008) of a cohort of children and adolescents from belarus exposed to radioiodines after the Chernobyl accident.

BACKGROUND: Recent studies of children and adolescents who were exposed to radioactive iodine-131 (I-131) after the 1986 Chernobyl nuclear accident in Ukraine exhibited a significant dose-related increase in the risk of thyroid cancer, but the association of radiation doses with tumor histologic and morphologic features is not clear. METHODS: A cohort of 11,664 individuals in Belarus who were aged ≤18 years at the time of the accident underwent 3 cycles of thyroid screening during 1997 to 2008. I-131 thyroid doses were estimated from individual thyroid activity measurements taken within 2 months after the accident and from dosimetric questionnaire data. Demographic, clinical, and tumor pathologic characteristics of the patients with thyroid cancer were analyzed using 1-way analysis of variance, chi-square tests or Fisher exact tests, and logistic regression. RESULTS: In total, 158 thyroid cancers were identified as a result of screening. The majority of patients had T1a and T1b tumors (93.7%), with many positive regional lymph nodes (N1; 60.6%) but few distant metastases (M1; CONCLUSIONS: I-131 thyroid radiation doses were associated with a significantly greater frequency of solid and diffuse sclerosing variants of thyroid cancer and various features of tumor aggressiveness

Risk of Thyroid Nodules in Residents of Belarus Exposed to Chernobyl Fallout as Children and Adolescents.

ContextAlthough radiation exposure is an important predictor of thyroid cancer on diagnosis of a thyroid nodule, the relationship between childhood radiation exposure and thyroid nodules has not been comprehensively evaluated.ObjectiveTo examine the association between internal I-131 thyroid dose and thyroid nodules in young adults exposed during childhood.Design, setting, and participantsIn this cross-sectional study, we screened residents of Belarus aged ≤18 years at the time of the Chernobyl nuclear accident for thyroid disease (median age, 21 years) with thyroid palpation, ultrasonography, blood/urine analysis, and medical follow-up when appropriate. Eligible participants (N = 11,421) had intact thyroid glands and doses based on direct individual thyroid activity measurements.Main outcome measuresExcess odds ratios per Gray (EOR/Gy, scaled at age 5 years at exposure) for any thyroid nodule and for nodules grouped by cytology/histology, diameter size, and singularity.ResultsRisk of any thyroid nodule increased significantly with I-131 dose and, for a given dose, with younger age at exposure. The EOR/Gy (95% confidence intervals) for neoplastic nodules (3.82; 0.87 to 15.52) was significantly higher than for nonneoplastic nodules (0.32; &lt;0.03 to 0.70) and did not vary by size; whereas the EOR/Gy for nonneoplastic nodules did vary by size (P = 0.02) and was 1.55 (0.36 to 5.46) for nodules ≥10 mm and 0.02 (&lt;-0.02 to 0.70) for nodules &lt;10 mm. EORs/Gy for single and multiple nodules were comparable.ConclusionsChildhood exposure to internal I-131 is associated with increased risk of neoplastic thyroid nodules of any size and nonneoplastic nodules ≥10 mm

Risk of Thyroid Nodules in Residents of Belarus Exposed to Chernobyl Fallout as Children and Adolescents.

ContextAlthough radiation exposure is an important predictor of thyroid cancer on diagnosis of a thyroid nodule, the relationship between childhood radiation exposure and thyroid nodules has not been comprehensively evaluated.ObjectiveTo examine the association between internal I-131 thyroid dose and thyroid nodules in young adults exposed during childhood.Design, setting, and participantsIn this cross-sectional study, we screened residents of Belarus aged ≤18 years at the time of the Chernobyl nuclear accident for thyroid disease (median age, 21 years) with thyroid palpation, ultrasonography, blood/urine analysis, and medical follow-up when appropriate. Eligible participants (N = 11,421) had intact thyroid glands and doses based on direct individual thyroid activity measurements.Main outcome measuresExcess odds ratios per Gray (EOR/Gy, scaled at age 5 years at exposure) for any thyroid nodule and for nodules grouped by cytology/histology, diameter size, and singularity.ResultsRisk of any thyroid nodule increased significantly with I-131 dose and, for a given dose, with younger age at exposure. The EOR/Gy (95% confidence intervals) for neoplastic nodules (3.82; 0.87 to 15.52) was significantly higher than for nonneoplastic nodules (0.32; &lt;0.03 to 0.70) and did not vary by size; whereas the EOR/Gy for nonneoplastic nodules did vary by size (P = 0.02) and was 1.55 (0.36 to 5.46) for nodules ≥10 mm and 0.02 (&lt;-0.02 to 0.70) for nodules &lt;10 mm. EORs/Gy for single and multiple nodules were comparable.ConclusionsChildhood exposure to internal I-131 is associated with increased risk of neoplastic thyroid nodules of any size and nonneoplastic nodules ≥10 mm

Risk of Thyroid Follicular Adenoma Among Children and Adolescents in Belarus Exposed to Iodine-131 After the Chornobyl Accident

Several studies reported an increased risk of thyroid cancer in children and adolescents exposed to radioactive iodines, chiefly iodine-131 ((131)I), after the 1986 Chornobyl (Ukrainian spelling) nuclear power plant accident. The risk of benign thyroid tumors following such radiation exposure is much less well known. We have previously reported a novel finding of significantly increased risk of thyroid follicular adenoma in a screening study of children and adolescents exposed to the Chornobyl fallout in Ukraine. To verify this finding, we analyzed baseline screening data from a cohort of 11,613 individuals aged ≤18 years at the time of the accident in Belarus (mean age at screening = 21 years). All participants had individual (131)I doses estimated from thyroid radioactivity measurements and were screened according to a standardized protocol. We found a significant linear dose response for 38 pathologically confirmed follicular adenoma cases. The excess odds ratio per gray of 2.22 (95% confidence interval: 0.41, 13.1) was similar in males and females but decreased significantly with increasing age at exposure (P < 0.01), with the highest radiation risks estimated for those exposed at <2 years of age. Follicular adenoma radiation risks were not significantly modified by most indicators of past and current iodine deficiency. The present study confirms the (131)I-associated increases in risk of follicular adenoma in the Ukrainian population and adds new evidence on the risk increasing with decreasing age at exposure