Studies of Thyroid Abnormalities in Northeastern Kazakhstan Associated With Nuclear Weapons Testing
Condition: Thyroid Cancer
MeSH terms: Thyroid Diseases
Study type: Observational

Summary: 
      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. 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 second part will involve thyroid screening by ultrasound in selected villages. The
      population to be screened will comprise 100-1500 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.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Retrospective
Keywords: Biodosimetry; Dose Reconstruction; Radioactive Fallout; Thyroid Screening; Ultrasound