Ihor J. Masnyk

A Cohort Study of Thyroid Cancer and Other Thyroid Diseases after the Chornobyl Accident: Objectives, Design and Methods

Abstract Chornobyl Thyroid Diseases Study Group of Belarus, Ukraine, and the USA. A Cohort Study of Thyroid Cancer and Other Thyroid Diseases after the Chornobyl Accident: Objectives, Design and Methods. Radiat. Res. 161, 481–492 (2004). The thyroid gland in children is one of the organs that is most sensitive to external exposure to X and γ rays. However, data on the risk of thyroid cancer in children after exposure to radioactive iodines are sparse. The Chornobyl accident in Ukraine in 1986 led to the exposure of large populations to radioactive iodines, particularly 131I. This paper describes an ongoing cohort study being conducted in Belarus and Ukraine that includes 25,161 subjects under the age of 18 years in 1986 who are being screened for thyroid diseases every 2 years. Individual thyroid doses are being estimated for all study subjects based on measurement of the radioactivity of the thyroid gland made in 1986 together with a radioecological model and interview data. Approximately 100 histologically confirmed thyroid cancers were detected as a consequence of the first round of screening. The data will enable fitting appropriate dose–response models, which are important in both radiation epidemiology and public health for prediction of risks from exposure to radioactive iodines from medical sources and any future nuclear accidents. Plans are to continue to follow-up the cohort for at least three screening cycles, which will lead to more precise estimates of risk.

The Ukrainian-American study of leukemia and related disorders among Chornobyl cleanup workers from Ukraine: III. Radiation risks.

Abstract 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).

Effect of long-term freezer storage, thawing, and refreezing on selected constituents of serum.

We determined the effect of long-term freezer storage and repeated thawing and freezing of serum on concentrations of electrolytes (sodium, potassium, calcium, and phosphate), enzymes (aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, and creatine kinase), total protein, tumor markers (carcinoembryonic antigen and alpha-fetoprotein), and other substances. Vials (1 ml) of frozen serum from a single blood drawing from 40 women with no breast disease and 70 with benign breast disease were analyzed annually from 1983 to 1987. Blood had been obtained from 40 subjects in 1978, 40 in 1980, and 30 in 1983. Thawing and refreezing studies were done in two ways: (1) serum samples from 30 subjects with benign breast disease were thawed at weekly intervals for 6 weeks and (2) serum samples from 30 patients with stage IV breast cancer were analyzed for alpha-fetoprotein and carcinoembryonic antigen, and serum specimens from 23 patients with benign breast disease and 7 control subjects were analyzed for lactate dehydrogenase and creatine kinase after thawing and keeping the samples at room temperature for up to 4 hours and then refreezing them. For measuring laboratory variability, duplicate samples were processed. Long-term storage (up to 10 years) and repeated thawing and refreezing did not affect the results of any tested constituents of serum. Although most measurements showed statistically significant variability over test cycles, these differences were thought to be due to laboratory variability.

Subclinical hypothyroidism after radioiodine exposure: Ukrainian-American cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident (1998-2000).

Background Hypothyroidism is the most common thyroid abnormality in patients treated with high doses of iodine-131 (131I). Data on risk of hypothyroidism from low to moderate 131I thyroid doses are limited and inconsistent. Objective This study was conducted to quantify the risk of hypothyroidism prevalence in relation to 131I doses received because of the Chornobyl accident. Methods This is a cross-sectional (1998–2000) screening study of thyroid diseases in a cohort of 11,853 individuals < 18 years of age at the time of the accident, with individual thyroid radioactivity measurements taken within 2 months of the accident. We measured thyroid-stimulating hormone (TSH), free thyroxine, and antibodies to thyroid peroxidase (ATPO) in serum. Results Mean age at examination of the analysis cohort was 21.6 years (range, 12.2–32.5 years), with 49% females. Mean 131I thyroid dose was 0.79 Gy (range, 0–40.7 Gy). There were 719 cases with hypothyroidism (TSH > 4 mIU/L), including 14 with overt hypothyroidism. We found a significant, small association between 131I thyroid doses and prevalent hypothyroidism, with the excess odds ratio (EOR) per gray of 0.10 (95% confidence interval, 0.03–0.21). EOR per gray was higher in individuals with ATPO ≤ 60 U/mL compared with individuals with ATPO > 60 U/mL (p < 0.001). Conclusions This is the first study to find a significant relationship between prevalence of hypothyroidism and individual 131I thyroid doses due to environmental exposure. The radiation increase in hypothyroidism was small (10% per Gy) and limited largely to subclinical hypothyroidism. Prospective data are needed to evaluate the dynamics of radiation-related hypothyroidism and clarify the role of antithyroid antibodies.

Identification of breast cancer patients with high risk of early recurrence after radical mastectomy: III. Steroid hormones measured in urine

The relationship of the levels of selected urinary steroid metabolites to breast cancer recurrence after radical mastectomy was studied. An analysis of variance of the steroid measurements suggested that the measurements standardized to per gram of creatinine were the appropriate measure to use in exploring these relationships. No significant associations were found for premenopausal patients; however, for postmenopausal patients, low levels of total 17‐ketosteroids were associated with a reduced two‐year recurrence‐free rate whereas low and high levels of OHA and high levels of total estrogens were associated with a relatively high two‐year recurrence‐free rate. Because of the large number of significance tests performed and the lack of consistent patterns, it is questionable whether the observed associations are of any importance. Including these steroid quantities in a multivariate regression model along with previously determined clinical prognostic factors indicated that the steroid determinations were the least important variables and did not make a significant contribution to the fit of the model.

Factors associated with elevated serum concentrations of anti-TPO antibodies in subjects with and without diffuse goitre. Results from the Ukrainian-American Cohort Study of thyroid cancer and other thyroid diseases following the Chornobyl accident.

Objectives  To examine factors associated with the prevalence of elevated anti‐thyroid peroxidase antibodies (ATPO) among iodine‐deficient adolescents and young adults and test whether associations vary according to the presence of diffuse goitre.