Microarray comparative genomic hybridization reveals genome-wide patterns of DNA gains and losses in post-Chernobyl thyroid cancer.

Genetic gains and losses resulting from DNA strand breakage by ionizing radiation have been demonstrated in vitro and suspected in radiation-associated thyroid cancer. We hypothesized that copy number deviations might be more prevalent, and/or occur in genomic patterns, in tumors associated with presumptive DNA strand breakage from radiation exposure than in their spontaneous counterparts. We used cDNA microarray-based comparative genome hybridization to obtain genome-wide, high-resolution copy number profiles at 14,573 genomic loci in 23 post-Chernobyl and 20 spontaneous thyroid cancers. The prevalence of DNA gains in tumors from cases in exposed individuals was two- to fourfold higher than for cases in unexposed individuals and up to 10-fold higher for the subset of recurrent gains. DNA losses for all cases were low and more prevalent in spontaneous cases. We identified unique patterns of copy variation (mostly gains) that depended on a history of radiation exposure. Exposed cases, especially the young, harbored more recurrent gains that covered more of the genome. The largest regions, spanning 1.2 to 4.9 Mbp, were located at 1p36.32-.33, 2p23.2-.3, 3p21.1-.31, 6p22.1-.2, 7q36.1, 8q24.3, 9q34.11, 9q34.3, 11p15.5, 11q13.2-12.3, 14q32.33, 16p13.3, 16p11.2, 16q21-q12.2, 17q25.1, 19p13.31-qter, 22q11.21 and 22q13.2. Copy number changes, particularly gains, in post-Chernobyl thyroid cancer are influenced by radiation exposure and age at exposure, in addition to the neoplastic process.

Non-cancer thyroid diseases among children in the Kaluga and Bryansk regions of the Russian Federation exposed to radiation following the Chernobyl accident.

This paper presents results of estimated radiation risks of non-cancer thyroid diseases in the people from Kaluga and Bryansk regions of the Russian Federation exposed in their childhood to radioiodine as a result of the Chernobyl accident. This work was carried out under the Joint Medical Research Project on non-cancer thyroid diseases conducted by Sasakawa Memorial Health Foundation and the Medical Radiological Research Center of the Russian Academy of Medical Sciences. The subjects were 2,457 people who underwent health examinations from 1997 to the end of 1999 who had individual radiometric thyroid data obtained between May and June 1986 and were aged 10 y or less at the time of exposure. The thyroid absorbed doses from incorporated 131I were estimated on the basis of measurements of exposure dose rate in the vicinity of the subject's thyroid and liver. A compartment model accounting for 131I metabolism in humans and cows was used. The estimated dose varied from 0 to 6 Gy, and its distribution was approximately lognormal with a mean of 0.132 Gy and standard deviation of 0.45 Gy. The prevalence of diffuse goiter in males showed a significant dose-response (p = 0.03) with an estimated odds ratio 1.36 at 1 Gy.