Retrospective radiation dose estimations, whether based on physical or biological measurements, or on theoretical dose reconstruction, are limited in their precision and reliability, particularly for exposures that occurred many decades ago. Here, we studied living U.S. military test participants, believed to have received high-dose radiation exposures during nuclear testing-related activities approximately six decades ago, with two primary goals in mind. The first was to compare three different approaches of assessing past radiation exposures: 1. Historical personnel monitoring data alone; 2. Dose reconstruction based on varying levels of completeness of individual information, which can include film badge data; and 3. Retrospective biodosimetry using chromosome aberrations in peripheral blood lymphocytes. The second goal was to use the collected data to make the best possible estimates of bone marrow dose received by a group with the highest military recorded radiation doses of any currently living military test participants. Six nuclear test participants studied had been on Rongerik Atoll during the 1954 CASTLE Bravo nuclear test. Another six were present at the Nevada Test Site (NTS) and/or Pacific Proving Ground (PPG) and were believed to have received relatively high-dose exposures at those locations. All were interviewed, and all provided a blood sample for cytogenetic analysis. Military dose records for each test participant, as recorded in the Defense Threat Reduction Agency's Nuclear Test Review and Information System, were used as the basis for historical film badge records and provided exposure scenario information to estimate dose via dose reconstruction. Dose to bone marrow was also estimated utilizing directional genomic hybridization (dGH) for high-resolution detection of radiation-induced chromosomal translocations and inversions, the latter being demonstrated for the first time for the purpose of retrospective biodosimetry. As the true dose for each test participant is not known these many decades after exposure, this study gauged the congruence of different methods by assessing the degree of correlation and degree of systematic differences. Overall, the best agreement between methods, defined by statistically significant correlations and small systematic differences, was between doses estimated by a dose reconstruction methodology that exploited all the available individual detail and the biodosimetry methodology derived from a weighted average dose determined from chromosomal translocation and inversion rates. Employing such a strategy, we found that the Rongerik veterans who participated in this study appear to have received, on average, bone marrow equivalent doses on the order of 300–400 mSv, while the NTS/ PPG participants appear to have received approximately 250–300 mSv. The results show that even for nuclear events that occurred six decades in the past, biological signatures of exposure are still present, and when taken together, chromosomal translocations and inversions can serve as reliable retrospective biodosimeters, particularly on a group-average basis, when doses received are greater than statistically-determined detection limits for the biological assays used.

The Thyrotoxicosis Therapy Follow-up Study (TTFUS) is comprised of 35,593 hyperthyroid patients treated from the mid-1940s through the mid-1960s. One objective of the TTFUS was to evaluate the long-term effects of high-dose iodine-131 ( 131 I) treatment ( 1–4 ). In the TTFUS cohort, 23,020 patients were treated with 131 I, including 21,536 patients with Graves disease (GD), 1,203 patients with toxic nodular goiter (TNG) and 281 patients with unknown disease. The study population constituted the largest group of hyperthyroid patients ever examined in a single health risk study. The average number (±1 standard deviation) of 131 I treatments per patient was 1.7 ± 1.4 for the GD patients and 2.1 ± 2.1 for the TNG patients. The average total 131 I administered activity was 380 ± 360 MBq for GD patients and 640 ± 550 MBq for TNG patients. In this work, a biokinetic model for iodine was developed to derive organ residence times and to reconstruct the radiation-absorbed doses to the thyroid gland and to other organs resulting from administration of 131 I to hyperthyroid patients. Based on 131 I data for a small, kinetically well-characterized sub-cohort of patients, multivariate regression equations were developed to relate the numbers of disintegrations of 131 I in more than 50 organs and tissues to anatomical (thyroid mass) and clinical (percentage thyroid uptake and pulse rate) parameters. These equations were then applied to estimate the numbers of 131 I disintegrations in the organs and tissues of all other hyperthyroid patients in the TTFUS who were treated with 131 I. The reference voxel phantoms adopted by the International Commission on Radiological Protection (ICRP) were then used to calculate the absorbed doses in more than 20 organs and tissues of the body. As expected, the absorbed doses were found to be highest in the thyroid (arithmetic means of 120 and 140 Gy for GD and TNG patients, respectively). Absorbed doses in organs other than the thyroid were much smaller, with arithmetic means of 1.6 Gy, 1.5 Gy and 0.65 Gy for esophagus, thymus and salivary glands, respectively. The arithmetic mean doses to all other organs and tissues were more than 100 times less than those to the thyroid gland. To our knowledge, this work represents the most comprehensive study to date of the doses received by persons treated with 131 I for hyperthyroidism.

Deterministic thyroid radiation doses due to iodine-131 ( 131 I) intake were reconstructed in a previous article for 11,732 participants of the Belarusian–American cohort study of thyroid cancer and other thyroid diseases in individuals exposed during childhood or adolescence to fallout from the Chernobyl accident. The current article describes an assessment of uncertainties in reconstructed thyroid doses that accounts for the shared and unshared errors. Using a Monte Carlo simulation procedure, 1,000 sets of cohort thyroid doses due to 131 I intake were calculated. The arithmetic mean of the stochastic thyroid doses for the entire cohort was 0.68 Gy. For two-thirds of the cohort the arithmetic mean of individual stochastic thyroid doses was less than 0.5 Gy. The geometric standard deviation of stochastic doses varied among cohort members from 1.33 to 5.12 with an arithmetic mean of 1.76 and a geometric mean of 1.73. The uncertainties in thyroid dose were driven by the unshared errors associated with the estimates of values of thyroid mass and of the 131 I activity in the thyroid of the subject; the contribution of shared errors to the overall uncertainty was small. These multiple sets of cohort thyroid doses will be used to evaluate the radiation risks of thyroid cancer and noncancer thyroid diseases, taking into account the structure of the errors in the dose estimates.

Dosimetic uncertainties, particularly those that are shared among subgroups of a study population, can bias, distort or reduce the slope or significance of a dose response. Exposure estimates in studies of health risks from environmental radiation exposures are generally highly uncertain and thus, susceptible to these methodological limitations. An analysis was published in 2008 concerning radiation-related thyroid nodule prevalence in a study population of 2,994 villagers under the age of 21 years old between August 1949 and September 1962 and who lived downwind from the Semipalatinsk Nuclear Test Site in Kazakhstan. This dose-response analysis identified a statistically significant association between thyroid nodule prevalence and reconstructed doses of fallout-related internal and external radiation to the thyroid gland; however, the effects of dosimetric uncertainty were not evaluated since the doses were simple point “best estimates”. In this work, we revised the 2008 study by a comprehensive treatment of dosimetric uncertainties. Our present analysis improves upon the previous study, specifically by accounting for shared and unshared uncertainties in dose estimation and risk analysis, and differs from the 2008 analysis in the following ways: 1. The study population size was reduced from 2,994 to 2,376 subjects, removing 618 persons with uncertain residence histories; 2. Simulation of multiple population dose sets (vectors) was performed using a two-dimensional Monte Carlo dose estimation method; and 3. A Bayesian model averaging approach was employed for evaluating the dose response, explicitly accounting for large and complex uncertainty in dose estimation. The results were compared against conventional regression techniques. The Bayesian approach utilizes 5,000 independent realizations of population dose vectors, each of which corresponds to a set of conditional individual median internal and external doses for the 2,376 subjects. These 5,000 population dose vectors reflect uncertainties in dosimetric parameters, partly shared and partly independent, among individual members of the study population. Risk estimates for thyroid nodules from internal irradiation were higher than those published in 2008, which results, to the best of our knowledge, from explicitly accounting for dose uncertainty. In contrast to earlier findings, the use of Bayesian methods led to the conclusion that the biological effectiveness for internal and external dose was similar. Estimates of excess relative risk per unit dose (ERR/Gy) for males (177 thyroid nodule cases) were almost 30 times those for females (571 cases) and were similar to those reported for thyroid cancers related to childhood exposures to external and internal sources in other studies. For confirmed cases of papillary thyroid cancers (3 in males, 18 in females), the ERR/Gy was also comparable to risk estimates from other studies, but not significantly different from zero. These findings represent the first reported dose response for a radiation epidemiologic study considering all known sources of shared and unshared errors in dose estimation and using a Bayesian model averaging (BMA) method for analysis of the dose response.

The U.S. National Cancer Institute, in collaboration with the Belarusian Ministry of Health, is conducting a study of thyroid cancer and other thyroid diseases in a cohort of about 12,000 persons who were exposed to fallout from the Chernobyl accident in April 1986. The study subjects were 18 years old or younger at the time of exposure and resided in Belarus in the most contaminated areas of the Gomel and Mogilev Oblasts, as well as in the city of Minsk. All cohort members had at least one direct thyroid measurement made in April–June 1986. Individual data on residential history, consumption of milk, milk products and leafy vegetables as well as administration of stable iodine were collected for all cohort members by means of personal interviews conducted between 1996 and 2007. Based on the estimated 131 I activities in the thyroids, which were derived from the direct thyroid measurements, and on the responses to the questionnaires, individual thyroid doses from intakes of 131 I were reconstructed for all cohort members. In addition, radiation doses to the thyroid were estimated for the following minor exposure pathways: (a) intake of short-lived 132 I, 133 I and 132 Te by inhalation and ingestion; (b) external irradiation from radionuclides deposited on the ground; and (c) ingestion intake of 134 Cs and 137 Cs. Intake of 131 I was the major pathway for thyroid exposure; its mean contribution to the thyroid dose was 92%. The thyroid doses from 131 I intakes varied from 0.5 mGy to almost 33 Gy; the mean was estimated to be 0.58 Gy, while the median was 0.23 Gy. The reconstructed doses are being used to evaluate the risk of thyroid cancer and other thyroid diseases in the cohort.

Exposure to radioactive iodine ( 131 I) from atmospheric nuclear tests conducted in Nevada in the 1950s may have increased thyroid cancer risks. To investigate the long-term effects of this exposure, we analyzed data on thyroid cancer incidence (18,545 cases) from eight Surveillance, Epidemiology, and End Results (SEER) tumor registries for the period 1973–2004. Excess relative risks (ERR) per gray (Gy) for exposure received before age 15 were estimated by relating age-, birth year-, sex- and county-specific thyroid cancer rates to estimates of cumulative dose to the thyroid that take age into account. The estimated ERR per Gy for dose received before 1 year of age was 1.8 [95% confidence interval (CI), 0.5–3.2]. There was no evidence that this estimate declined with follow-up time or that risk increased with dose received at ages 1–15. These results confirm earlier findings based on less extensive data for the period 1973–1994. The lack of a dose response for those exposed at ages 1–15 is inconsistent with studies of children exposed to external radiation or 131 I from the Chernobyl accident, and results need to be interpreted in light of limitations and biases inherent in ecological studies, including the error in doses and case ascertainment resulting from migration. Nevertheless, the study adds support for an increased risk of thyroid cancer due to fallout, although the data are inadequate to quantify it.

Sigurdson, A. J., Land, C. E., Bhatti, P., Pineda, M., Brenner, A., Carr, Z., Gusev, B. I., Zhumadilov, Z., Simon, S. L., Bouville, A., Rutter, J. L., Ron, E. and Struewing, J. P. Thyroid Nodules, Polymorphic Variants in DNA Repair and RET -Related Genes, and Interaction with Ionizing Radiation Exposure from Nuclear Tests in Kazakhstan. Radiat. Res. 171, 77–88 (2009). Risk factors for thyroid cancer remain largely unknown except for ionizing radiation exposure during childhood and a history of benign thyroid nodules. Because thyroid nodules are more common than thyroid cancers and are associated with thyroid cancer risk, we evaluated several polymorphisms potentially relevant to thyroid tumors and assessed interaction with ionizing radiation exposure to the thyroid gland. Thyroid nodules were detected in 1998 by ultrasound screening of 2997 persons who lived near the Semipalatinsk nuclear test site in Kazakhstan when they were children (1949–1962). Cases with thyroid nodules ( n = 907) were frequency matched (1:1) to those without nodules by ethnicity (Kazakh or Russian), gender and age at screening. Thyroid gland radiation doses were estimated from fallout deposition patterns, residence history and diet. We analyzed 23 polymorphisms in 13 genes and assessed interaction with ionizing radiation exposure using likelihood ratio tests (LRT). Elevated thyroid nodule risks were associated with the minor alleles of RET S836S (rs1800862, P = 0.03) and GFRA1 −193C>G (rs not assigned, P = 0.05) and decreased risk with XRCC1 R194W (rs1799782, P trend = 0.03) and TGFB1 T263I (rs1800472, P = 0.009). Similar patterns of association were observed for a small number of papillary thyroid cancers ( n = 25). Ionizing radiation exposure to the thyroid gland was associated with significantly increased risk of thyroid nodules (age and gender adjusted excess odds ratio/Gy = 0.30, 95% CI 0.05–0.56), with evidence for interaction by genotype found for XRCC1 R194W (LRT P value = 0.02). Polymorphisms in RET signaling, DNA repair and proliferation genes may be related to risk of thyroid nodules, consistent with some previous reports on thyroid cancer. Borderline support for gene-radiation interaction was found for a variant in XRCC1, a key base excision repair protein. Other pathways such as genes in double-strand break repair, apoptosis and genes related to proliferation should also be pursued.

Romanenko, A. Ye., Finch, S. C., Hatch, M., Lubin, J. H., Bebeshko, V. G., Bazyka, D. A., Gudzenko, N., Dyagil, I. S., Reiss, R. F., Bouville, A., Chumak, V. V., Trotsiuk, N. K., Babkina, N. G., Belyayev, Yu., Masnyk, I., Ron, E., Howe, G.;thR. and Zablotska, L. B. The Ukrainian-American Study of Leukemia and Related Disorders among Chornobyl Cleanup Workers from Ukraine: III. Radiation Risks. Radiat. Res. 170, 711–720 (2008). Leukemia is one of the cancers most susceptible to induction by ionizing radiation, but the effects of lower doses delivered over time have not been quantified adequately. After the Chornobyl (Chernobyl) accident in Ukraine in April 1986, several hundred thousand workers who were involved in cleaning up the site and its surroundings received fractionated exposure, primarily from external γ radiation. To increase our understanding of the role of protracted low-dose radiation exposure in the etiology of leukemia, we conducted a nested case-control study of leukemia in a cohort of cleanup workers identified from the Chornobyl State Registry of Ukraine. The analysis is based on 71 cases of histologically confirmed leukemia diagnosed in 1986–2000 and 501 age- and residence-matched controls selected from the same cohort. Study subjects or their proxies were interviewed about their cleanup activities and other relevant factors. Individual bone marrow radiation doses were estimated by the RADRUE dose reconstruction method (mean dose = 76.4 mGy, SD = 213.4). We used conditional logistic regression to estimate leukemia risks. The excess relative risk (ERR) of total leukemia was 3.44 per Gy [95% confidence interval (CI) 0.47–9.78, P < 0.01]. The dose response was linear and did not differ significantly by calendar period of first work in the 30-km Chornobyl zone, duration or type of work. We found a similar dose–response relationship for chronic and non-chronic lymphocytic leukemia [ERR = 4.09 per Gy (95% CI < 0–14.41) and 2.73 per Gy (95% CI < 0–13.50), respectively]. To further clarify these issues, we are extending the case-control study to ascertain cases for another 6 years (2001–2006).

Kesminiene, A., Evrard, A-S., Ivanov, V. K., Malakhova, I. V., Kurtinaitis, J., Stengrevics, A., Tekkel, M., Anspaugh, L. R., Bouville, A., Chekin, S., Chumak, V. V., Drozdovitch, V., Gapanovich, V., Golovanov, I., Hubert, P., Illichev, S. V., Khait, S. E., Kryuchkov, V. P., Maceika, E., Maksyoutov, M., Mirkhaidarov, A. K., Polyakov, S., Shchukina, N., Tenet, V., Tserakhovich, T. I., Tsykalo, A., Tukov, A. R. and Cardis, E. Risk of Hematological Malignancies among Chernobyl Liquidators. Radiat. Res. 170, 721–735 (2008). A case-control study of hematological malignancies was conducted among Chernobyl liquidators (accident recovery workers) from Belarus, Russia and Baltic countries to assess the effect of low- to medium-dose protracted radiation exposures on the relative risk of these diseases. The study was nested within cohorts of liquidators who had worked around the Chernobyl plant in 1986–1987. A total of 117 cases [69 leukemia, 34 non-Hodgkin lymphoma (NHL) and 14 other malignancies of lymphoid and hematopoietic tissue] and 481 matched controls were included in the study. Individual dose to the bone marrow and uncertainties were estimated for each subject. The main analyses were restricted to 70 cases (40 leukemia, 20 NHL and 10 other) and their 287 matched controls with reliable information on work in the Chernobyl area. Most subjects received very low doses (median 13 mGy). For all diagnoses combined, a significantly elevated OR was seen at doses of 200 mGy and above. The excess relative risk (ERR) per 100 mGy was 0.60 [90% confidence interval (CI) −0.02, 2.35]. The corresponding estimate for leukemia excluding chronic lymphoid leukemia (CLL) was 0.50 (90% CI −0.38, 5.7). It is slightly higher than but statistically compatible with those estimated from A-bomb survivors and recent low-dose-rate studies. Although sensitivity analyses showed generally similar results, we cannot rule out the possibility that biases and uncertainties could have led to over- or underestimation of the risk in this study.

Chumak, V. V., Romanenko, A. Y., Voillequé, P. G., Bakhanova, E. V., Gudzenko, N., Hatch, M., Zablotska, L. B., Golovanov, I. A., Luckyanov, N. K., Sholom, S. V., Kryuchkov, V. P. and Bouville, A. The Ukrainian-American Study of Leukemia and Related Disorders among Chornobyl Cleanup Workers from Ukraine: II. Estimation of Bone Marrow Doses. Radiat. Res. 170, 698–710 (2008). After the accident that took place on 26 April 1986 at the Chornobyl nuclear power plant, hundreds of thousands of cleanup workers were involved in emergency measures and decontamination activities. In the framework of an epidemiological study of leukemia and other related blood diseases among Ukrainian cleanup workers, individual bone marrow doses have been estimated for 572 cases and controls. Because dose records were available for only about half of the study subjects, a time-and-motion method of dose reconstruction that would be applicable to all study subjects, whether dead or alive, was developed. The doses were calculated in a stochastic mode, thus providing estimates of uncertainties. The arithmetic mean individual bone marrow doses were found to range from 0.00004 to 3,300 mGy, with an average value of 87 mGy over the 572 study subjects. The uncertainties, characterized by the geometric standard deviation of the probability distribution of the individual dose, varied from subject to subject and had a median value of about 2. These results should be treated as preliminary; it is likely that the dose calculations and particularly the uncertainty estimates will be improved in the follow-up of this effort.

Parveen, B., Preston, D. L., Doody, M. M., Hauptmann, M., Kampa, D., Alexander, B. H., Petibone, D., Simon, S. L., Weinstock, R. M., Bouville, A., Yong, L. C., Freedman, D. M., Mabuchi, K., Linet, M. S., Edwards, A. A., Tucker, J. D. and Sigurdson, A. J. Retrospective Biodosimetry among United States Radiologic Technologists. Radiat. Res. 167, 727–734 (2007). Measurement of chromosome translocations in peripheral blood lymphocytes has been used to quantify prior exposure to ionizing radiation, including for workers exposed to low, chronic doses. We assessed translocation frequencies in a subset of U.S. radiologic technologists to substantiate ionizing radiation dose estimates developed for 110,418 technologists who worked between 1916 and 1984. From 3,441 cohort members known to have begun working before 1950, we selected a sample of 152, stratified by estimated cumulative dose, oversampling from higher-dose categories and excluding persons with a prior cancer diagnosis, a personal or family history of chromosomal instability disorders, or a current history of smoking. Estimates of film-badge dose ranged from less than 10 cSv to more than 30 cSv. Blood samples, obtained in 2004, were analyzed by fluorescence in situ hybridization (FISH) whole chromosome painting by simultaneously labeling chromosomes 1, 2 and 4 in red and 3, 5 and 6 in green. Translocations were scored in 1800 well-spread metaphase cells and expressed per 100 cell equivalents (CE) per person. Linear Poisson regression models with allowance for overdispersion were used to assess the relationship between estimated occupational red bone marrow absorbed dose in cGy and translocation frequency, adjusted for age, gender and estimated red bone marrow absorbed dose score from personal diagnostic procedures. We observed 0.09 excess translocations per 100 CE per cGy red bone marrow dose (95% CI: −0.01, 0.2; P = 0.07), which is similar to the expected estimate based on previous cytogenetic studies (0.05 excess translocations per 100 CE per cGy). Despite uncertainty in the estimates of occupational red bone marrow absorbed doses, we found good general agreement between the doses and translocation frequencies, lending support to the credibility of the dose assessment for this large cohort of U.S. radiologic technologists.

Bouville, A., Chumak, V. V., Inskip, P. D., Kryuchkov, V. and Luckyanov, N. The Chornobyl Accident: Estimation of Radiation Doses Received by the Baltic and Ukrainian Cleanup Workers. Radiat. Res. 166, 158–167 (2006). During the first day after the explosion, the Chornobyl accident of April 26, 1986 exposed a few hundred emergency workers to high dose levels ranging up to 16 Gy, resulting in acute radiation syndrome. Subsequently, several hundred thousand cleanup workers were sent to the Chornobyl power plant to mitigate the consequences of the accident. Depending on the nature of the work to be carried out, the cleanup workers were sent for periods ranging from several minutes to several months. The average dose from external radiation exposure that was received by the cleanup workers was about 170 mGy in 1986 and decreased from year to year. The radiation exposure was mainly due to external irradiation from γ-ray-emitting radionuclides and was relatively homogeneous over all organs and tissues of the body. To assess the possible health consequences of external irradiation at relatively low dose rates, the U.S. National Cancer Institute is involved in two studies of Chornobyl cleanup workers: (1) a study of cancer incidence and thyroid disease among Estonian, Latvian and Lithuanian workers, and (2) a study of leukemia and other related blood diseases among Ukrainian workers. After an overview of the sources of exposure and of the radiation doses received by the cleanup workers, a description of the efforts made to estimate individual doses in the Baltic and Ukrainian studies is presented.

Beck, H. L., Anspaugh, L. R., Bouville, A. and Simon, S. L. Review of Methods of Dose Estimation for Epidemiological Studies of the Radiological Impact of Nevada Test Site and Global Fallout. Radiat. Res. 166, 209–218 (2006). Methods to assess radiation doses from nuclear weapons test fallout have been used to estimate doses to populations and individuals in a number of studies. However, only a few epidemiology studies have relied on fallout dose estimates. Though the methods for assessing doses from local and regional compared to global fallout are similar, there are significant differences in predicted doses and contributing radionuclides depending on the source of the fallout, e.g. whether the nuclear debris originated in Nevada at the U.S. nuclear test site or whether it originated at other locations worldwide. The sparse historical measurement data available are generally sufficient to estimate external exposure doses reasonably well. However, reconstruction of doses to body organs from ingestion and inhalation of radionuclides is significantly more complex and is almost always more uncertain than are external dose estimates. Internal dose estimates are generally based on estimates of the ground deposition per unit area of specific radionuclides and subsequent transport of radionuclides through the food chain. A number of technical challenges to correctly modeling deposition of fallout under wet and dry atmospheric conditions still remain, particularly at close-in locations where sizes of deposited particles vary significantly over modest changes in distance. This paper summarizes the various methods of dose estimation from weapons test fallout and the most important dose assessment and epidemiology studies that have relied on those methods.

Simon, S. L., Weinstock, R. M., Doody, M. M., Neton, J., Wenzel, T., Stewart, P., Mohan, A. K., Yoder, C., Freedman, M., Hauptmann, M., Bouville, A., Cardarelli, J., Feng, H. A. and Linet, M. Estimating Historical Radiation Doses to a Cohort of U.S. Radiologic Technologists. Radiat. Res. 166, 174– 192 (2006). Data have been collected and physical and statistical models have been constructed to estimate unknown occupational radiation doses among 90,000 members of the U.S. Radiologic Technologists cohort who responded to a baseline questionnaire during the mid-1980s. Since the availability of radiation dose data differed by calendar period, different models were developed and applied for years worked before 1960, 1960– 1976 and 1977–1984. The dose estimation used available film-badge measurements (approximately 350,000) for individual cohort members, information provided by the technologists on their work history and protection practices, and measurement and other data derived from the literature. The dosimetry model estimates annual and cumulative occupational badge doses (personal dose equivalent) for each technologist for each year worked from 1916 through 1984 as well as absorbed doses to organs and tissues including bone marrow, female breast, thyroid, ovary, testes, lung and skin. Assumptions have been made about critical variables including average energy of X rays, use of protective aprons, position of film badges, and minimum detectable doses. Uncertainty of badge and organ doses was characterized for each year of each technologist's working career. Monte Carlo methods were used to generate estimates of cumulative organ doses for preliminary cancer risk analyses. The models and predictions presented here, while continuing to be modified and improved, represent one of the most comprehensive dose reconstructions undertaken to date for a large cohort of medical radiation workers.

The accident at the Chernobyl nuclear power plant on April 26, 1986, released approximately 2 EB1 of 131 I and other radioiodine isotopes that heavily contaminated southern Belarus. An increase in thyroid cancer reported in 1992 and attributed to the Chernobyl accident was challenged as possibly the result of intensive screening. We began a case-control study to test the hypothesis that the Chernobyl accident caused the increase in thyroid cancer. Records of childhood thyroid cancer in the national therapy centers in Minsk in 1992 yielded 107 individuals with confirmed pathology diagnoses and available for interview. Pathways to diagnosis were (1) routine endocrinological screening in 63, (2) presentation with enlarged or nodular thyroid in 25 and (3) an incidental finding in 19. Two sets of controls were chosen, one matched on pathway to diagnosis, the other representing the area of heavy fallout, both matched on age, sex and rural/urban residence in 1986. The 131 I dose to the thyroid was estimated from ground deposition of 137 Cs, ground deposition of 131 I, a data bank of 1986 thyroid radiation measurements, questionnaires and interviews. Highly significant differences were observed between cases and controls (both sets) with respect to dose. The differences persisted within pathway to diagnosis, gender, age and year of diagnosis, and level of iodine in the soil, and were most marked in the southern portion of the Gomel region. The case-control comparisons indicate a strong relationship between thyroid cancer and estimated radiation dose from the Chernobyl accident.