Impact of uncertainties in exposure assessment on estimates of thyroid cancer risk among Ukrainian children and adolescents exposed from the chernobyl accident

The 1986 accident at the Chernobyl nuclear power plant remains the most serious nuclear accident in history, and excess thyroid cancers, particularly among those exposed to releases of iodine-131 remain the best-documented sequelae. Failure to take dose-measurement error into account can lead to bias in assessments of dose-response slope. Although risks in the Ukrainian-US thyroid screening study have been previously evaluated, errors in dose assessments have not been addressed hitherto. Dose-response patterns were examined in a thyroid screening prevalence cohort of 13,127 persons aged <18 at the time of the accident who were resident in the most radioactively contaminated regions of Ukraine. We extended earlier analyses in this cohort by adjusting for dose error in the recently developed TD-10 dosimetry. Three methods of statistical correction, via two types of regression calibration, and Monte Carlo maximum-likelihood, were applied to the doses that can be derived from the ratio of thyroid activity to thyroid mass. The two components that make up this ratio have different types of error, Berkson error for thyroid mass and classical error for thyroid activity. The first regression-calibration method yielded estimates of excess odds ratio of 5.78 Gy-1 (95% CI 1.92, 27.04), about 7% higher than estimates unadjusted for dose error. The second regression-calibration method gave an excess odds ratio of 4.78 Gy-1 (95% CI 1.64, 19.69), about 11% lower than unadjusted analysis. The Monte Carlo maximum-likelihood method produced an excess odds ratio of 4.93 Gy-1 (95% CI 1.67, 19.90), about 8% lower than unadjusted analysis. There are borderline-significant (p= 0.101-0.112) indications of downward curvature in the dose response, allowing for which nearly doubled the low-dose linear coefficient. In conclusion, dose-error adjustment has comparatively modest effects on regression parameters, a consequence of the relatively small errors, of a mixture of Berkson and classical form, associated with thyroid dose assessment

I-131 Dose Response for Incident Thyroid Cancers in Ukraine Related to the Chornobyl Accident

Background: Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case–control studies, and studies of prevalent cancers

Factors associated with serum thyroglobulin in a Ukrainian cohort exposed to iodine-131 from the accident at the Chernobyl Nuclear Plant.

BackgroundSerum thyroglobulin (Tg) is associated with the presence of thyroid disease and has been proposed as a biomarker of iodine status. Few studies have examined factors related to serum Tg in populations environmentally exposed to ionizing radiation and living in regions with endemic mild-to-moderate iodine deficiency.MethodsWe screened 10,430 individuals who were living in Ukraine and under 18 years of age at the time of the 1986 Chernobyl Nuclear Power Plant accident for thyroid disease from 2001 to 2003. We estimated the percent change (PC) in serum Tg associated with demographic factors, iodine-131 thyroid dose, and indicators of thyroid structure and function using linear regression. We also examined these relationships for individuals with and without indications of thyroid abnormality.ResultsMean and median serum Tg levels were higher among participants with abnormal thyroid structure/function. Percent change in serum Tg increased among females, smokers and with older age (p-values&lt;0.001), and Tg increased with increasing thyroid volume, and serum thyrotropin (p-values for trend&lt;0.001). We found no evidence of significant associations between iodine-131 thyroid dose and Tg. Serum Tg levels were inversely associated with iodized salt intake (PC=-7.90, 95% confidence interval: -12.08, -3.52), and over the range of urinary iodine concentration, the odds of having elevated serum Tg showed a U-shaped curve with elevated Tg at low and high urinary iodine concentrations.ConclusionSerum Tg may be a useful indicator of population iodine status and a non-specific biomarker of structural and functional thyroid abnormalities in epidemiological studies

I-131 dose response for incident thyroid cancers in Ukraine related to the Chornobyl accident.

BackgroundCurrent knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case-control studies, and studies of prevalent cancers.ObjectiveTo address this limitation, we evaluated the dose-response relationship for incident thyroid cancers using measurement-based individual iodine-131 (I-131) thyroid dose estimates in a prospective analytic cohort study.MethodsThe cohort consists of individuals &lt; 18 years of age on 26 April 1986 who resided in three contaminated oblasts (states) of Ukraine and underwent up to four thyroid screening examinations between 1998 and 2007 (n = 12,514). Thyroid doses of I-131 were estimated based on individual radioactivity measurements taken within 2 months after the accident, environmental transport models, and interview data. Excess radiation risks were estimated using Poisson regression models.ResultsSixty-five incident thyroid cancers were diagnosed during the second through fourth screenings and 73,004 person-years (PY) of observation. The dose-response relationship was consistent with linearity on relative and absolute scales, although the excess relative risk (ERR) model described data better than did the excess absolute risk (EAR) model. The ERR per gray was 1.91 [95% confidence interval (CI), 0.43-6.34], and the EAR per 10⁴ PY/Gy was 2.21 (95% CI, 0.04-5.78). The ERR per gray varied significantly by oblast of residence but not by time since exposure, use of iodine prophylaxis, iodine status, sex, age, or tumor size.ConclusionsI-131-related thyroid cancer risks persisted for two decades after exposure, with no evidence of decrease during the observation period. The radiation risks, although smaller, are compatible with those of retrospective and ecological post-Chornobyl studies

Distribution of the geometric standard deviation (GSD) of errors associated with assessments of thyroid activity GSD as a function of TD-10 thyroid dose.

<p>Low dose range.</p

Variation of excess relative risk with age at the time of the accident (using 1^st regression calibration method, adapted from Kukush <i>et al.</i>[13]).

<p>Other details as for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085723#pone-0085723-g004" target="_blank">Figure 4</a>.</p