Trial Information

Studies of Thyroid Abnormalities in Northeastern Kazakhstan Associated With Nuclear Weapons Testing

We propose to study the prevalence of thyroid nodules and cancer in relation to radiation
dose, in a defined cohort of Kazakhstan residents exposed as children to radioactive fallout
from atomic bomb tests at the neighboring Semipalatinsk Test Site (STS). The population
near the STS is believed to have received radiation doses from fallout that were much higher
than that experienced by any population of comparable size in the US. The study population
is a defined cohort of 20,000 residents, half of whom, in 1960, resided in heavily-exposed
villages; the other half lived in lightly-exposed villages. The population is rural, with a
diet that was and is heavily dependent upon fresh milk from household or local cows and
therefore likely to have led to ingestion of radioactive iodine from fallout. The study is
two parts.

The first part involves a cytogenetic assay for radiation biodosimetry purposes of
peripheral lymphocytes obtained from blood samples donated by 40 cohort members with
individuals radiation dose estimates, and electron paramagnetic resonance (EPR) assays of
about 110 stored tooth samples. The two techniques are complementary. Blood samples will
be collected from 25 putative high-dose and 15 low-dose cohort members and processed or
cytogenetic assay using fluorescent in situ hybridization (FISH) for stable chromosome
aberrations in peripheral lymphocytes. This biodosimetric validation assay, will be carried
out by Nailya Chaizhunusova, chief of cytogenetics at the Scientific research Institute for
Radiation Medicine and Ecology, in collaboration with Dr. Tracy Yang at the NASA Johnson
Space Center in Houston, Texas. It should be possible to detect gamma radiation doses as
low as 150 mGy.

The EPR investigation will take advantage of a repository of teeth extracted by local
dentists during medical and dental programs in 1966-67 and 1999, stored, and catalogued by
our collaborators in Kazakhstan (not in connection with this study). Tooth samples are
identified by village of exposure, but not individually within villages. However, the
identities of the donors, and therefore their ages and exposure histories, are known to our
collaborators in Kazakhstan; therefore it will be possible to compare the EPR results with
gamma dose estimates calculated on the basis of exposure history. It is intended that the
EPR assays will be carried out at the National Institute of Standards and Technology under a
purchase order agreement.

The second part will involve thyroid screening by ultrasound in selected villages. The
population to be screened will comprise 1000-1500 members of the study cohort exposed as
young children to high fallout levels, and equal numbers of comparable ages exposed to
little or no fallout. Fine needle aspiration biopsy will be performed, under separate
informed consent, if the palpation and ultrasound results suggest presence of a tumor.
Presence and malignancy of tumor will be determined by cytopathology. Subjects with
evidence of thyroid disease will be referred to thyroid specialists at the Semipalatinsk
State Medical Academy. Finger stick blood samples will be obtained to assess thyroid
function using RIA methods with coated tube technology for T4 and TSH. The most sensitive
statistical comparisons are expected to be dose-response analyses with respect to prevalence
of thyroid nodules, which are common and known to be associated with radiation dose.
Comparisons in terms of thyroid cancer, and benign and malignant neoplasms combined, are
likely to be less sensitive but of acceptable power if risks associated with chronic
radiation in this population are similar to those associated with acute exposure to X-ray or
gamma radiation in other populations.