Several years after a 1988 agreement between the United States and the USSR to cooperate in the area of nuclear reactor safety, the National Cancer Institute (NCI), NIH undertook to develop a study of leukemia risk among Ukrainian men potentially exposed to external radiation during clean-up operations (e.g., liquidators) following the Chernobyl accident. Responsibility for the study resides in the Radiation Epidemiology Branch of NCI.
Leukemia, a malignancy arising from the bone marrow, is strongly associated with radiation exposure because of the sensitivity of the bone marrow to the carcinogenic effects of external radiation. Leukemia is also among the earliest cancer sites to show an increase following radiation exposure, and one of the malignancies most consistently associated with external radiation exposure. Evaluating leukemia risk among the Chernobyl clean-up workers was important both in and of itself and also because of the information it would provide about risks to individuals in similar circumstances involving protracted exposure, such as nuclear workers.
Efforts to develop a research plan for studying leukemia among clean-up workers in Ukraine began as early as 1989-1990. A pilot phase, conducted between 1997-1999 to establish the feasibility of the proposed investigation, showed that a suitable cohort could be assembled and that representative clean-up workers could be located and interviewed regarding their experience during the clean-up operations. Leukemia cases were registered in hematologic facilities in central oblast dispensaries and the medical records were found to be readily available. A sample of 100 cases of leukemia and related disorders was collected and reviewed by an international group of hematologists and pathologists, with a high level of confirmation of the preliminary diagnoses made by local hematologists.
The cohort consists of approximately 110,000 clean-up workers in Ukraine who worked in the 30 km zone around the plant during 1986-1990 and resided in Kiev City or in one of the following oblasts: Cherkassy, Chernigov, Dnepropetrovsk, Kharkov, Kiev. The cohort was identified through the State Chernobyl Registry. In the first phase of the study, cases of leukemia and other hematologic disorders (specifically multiple myleoma and myelodysplasia ) were sought in all relevant health care institutions and assembled into a leukemia registry. Ultimately, record linkage was used to identify cases occurring among members of the cohort between 1987-2000. For each case, five controls were drawn from cohort members who did not develop hematologic disorders, matched to the case on age and area of residence. To gather information for estimating individual dose, detailed interviews are conducted to obtain data related to cumulative estimated dose to bone marrow. Estimated bone marrow doses based on a specially-developed time-and-motion approach have been evaluated in a statistical analysis (Romanenko et al., 2008) to evaluate the dose response relationship with leukemia risk overall, as well as with two separate subgroups: chronic lymphocytic leukemia (CLL, a hematologic malignancy generally thought not to be related to radiation exposure) and non-CLL cases.
The principal objective of the study is to evaluate whether there is a dose-related increase in risk of leukemia among the clean-up workers. Possible modifiers of risk such as age at exposure or time since exposure are of particular interest. Also of interest will be to compare the magnitude of the observed risk per unit dose from a protracted exposure with that seen in the atomic bomb survivors, who received an acute exposure.
The records of 28 health care institutions were searched and abstracted to assemble a list of cases occurring in the study time period. Linkage with the list of cohort members has yielded a total of 137 cases: 110 leukemia, 17 myelodysplasia and 10 multiple myelomas. For the approximately 100 deceased cases and controls, interviews with two proxy respondents are conducted: one with the spouse and one with at least one co-worker. An International Diagnostic Review Panel verified 86 leukemias.
Since only about half of the clean-up workers had official doses recorded, independent methods were evaluated for estimation of the doses based on environmental data combined with characteristics of individual exposures obtained through detailed interviews. In addition, laboratories were set up to implement new methods of biological dosimetry: Fluorescence in Situ Hybridization (FISH) technique on blood samples and Electron Paramagnetic Resonance (EPR) Spectroscopy measurements of tooth enamel. Both approaches proved to be helpful but not sensitive enough to measure the low doses that were received by a substantial number of clean-up workers. The current approach is to use a recently developed method called RADRUE (Radiation Dose Reconstruction with Uncertainty Estimates), based on the detailed interviews with the subjects. RADRUE provides estimates of subjects' bone marrow doses and of the attendant uncertainties.
A decision was made to accrue additional cases for the next six years, bringing the total time of follow-up to twenty years. This second phase uses the National Cancer Registry of Ukraine to identify the cases.
The ERR/Gy for all leukemia in the initial phase of the study was found to be 3.44/Gy (95% CI: 0.47, 9.78). Risk estimates were elevated for both types of cases (CLL: ERR/Gy=4.09; 95% CI: 0, 14.4, and non-CLL ERR/Gy=2.73;95% CI: 0, 13.5). A publication combining data from the initial and later phases of the leukemia study is in preparation.
The clean-up workers sent to the site and/or residing nearby in 1986-87 also sustained some exposure to internal radiation, raising the possibility that thyroid cancer risk might also be elevated in this population. We are completing a pilot study to investigate the feasibility of launching a new study to investigate this hypothesis in the liquidator cohort.
The study is based in Kiev, in the Research Center for Radiation Medicine, Academy of Medical Sciences of Ukraine and includes a collaboration with the National Cancer Registry of Ukraine.
The major benefit to Ukrainians and the scientific community at large is that the study will address concerns about the health effects of the accident on the workers who were involved with the clean-up. Other benefits include the establishment of a leukemia registry set up to identify all the cases that occurred during 1987-2000. A panel of international experts has provided local hematologists with a valuable opportunity for professional interaction. Publications describing the findings provide important new data \on the risks associated with low-dose, protracted exposure to external radiation.