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

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

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

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