Thus far there are relatively few data on the risk of leukemia among those who were exposed to external radiation during cleanup operations following the Chornobyl nuclear accident, and results have not been consistent. To investigate this issue further, we assembled a cohort of 110,645 male cleanup workers from Ukraine and identified cases of leukemia occurring during the period 1986 to 2000. Detailed interviews were conducted and individual bone marrow doses were estimated using a new time-and-motion method known as RADRUE (Realistic Analytical Dose Reconstruction with Uncertainty Estimate). See companion paper II for a detailed description of the dosimetry. For the initial analyses we used a nested case-control approach with a minimum of five controls per case, matched for year of birth, oblast (region) of registration and residence. All identified cases were reviewed by an international panel of experts.The dose-response analysis and results are given in companion paper III.
Acute myeloid leukemia (AML) can develop as a secondary malignancy following radiotherapy, but also following low-dose environmental or occupational radiation exposure. Therapy-related AML frequently carries deletions of chromosome 5q and/or 7, but for low-dose exposure associated AML this has not been described. For the present study we performed genome-wide screens for loss-of-heterozygosity (LOH) in a set of 19 AML cases that developed after radiation-exposure following the Chernobyl accident. Using Affymetrix SNP arrays we found large regions of LOH in 16 of the cases. Eight cases (42%) demonstrated LOH at 5q and/or 7, which is a known marker of complex karyotypic changes and poor prognosis. We could show here for the first time that exposure to low-dose ionizing radiation induces AML with molecular alterations similar to those seen in therapy-related cases.
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