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1.
Thyroid ; 18(8): 839-46, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18690796

ABSTRACT

BACKGROUND: Ionizing radiation is the strongest risk factor known for the development of thyroid neoplasia. While previous studies have demonstrated a high prevalence of ret/papillary thyroid cancer (PTC) activation in cohorts of patients developing thyroid nodules after childhood exposure to ionizing radiation, no study has directly compared ret/PTC activation with individual estimates of radiation dose to the thyroid. This study combines individual thyroid dosimetry data with molecular analysis of surgically removed thyroid nodules in order to determine if ret/PTC activation in thyroid nodules is associated with increasing estimated radiation dose from Chernobyl. METHODS: This pilot study included adults and children diagnosed with PTC (n = 76) and children diagnosed with follicular adenomas (n = 24) during May 1986 through December 1999, who were living in the Bryansk Oblast of the Russian Federation at the time of the Chernobyl accident, who had paraffin-embedded thyroid surgical samples available and for whom an individual dose to the thyroid could be estimated. The frequency of ret/PTC activation was determined using RT-PCR analysis. Individual radiation doses to the thyroid were estimated using a semiempirical model, and data were collected by detailed interview, primarily of the participant's mother. RESULTS: ret/PTC oncogene activation was detected in 23.8% (5/21) and 14.5% (8/55) of the childhood and adult PTC cases, respectively, and 8.3% (2/24) of the follicular adenoma cases. No statistically significant differences were noted in age at the time of exposure or diagnosis, gender, latency period, or estimated radiation dose between PTC patients with or without ret/PTC activation. Further, no significant dose-response relationship was detected among PTC patients with ret/PTC activation. CONCLUSIONS: Factors other than individual thyroid radiation doses may influence the development and subsequent detection of ret/PTC oncogene activation in radiation related PTC arising in the Bryansk Oblast of the Russian Federation in the aftermath of the Chernobyl accident.


Subject(s)
Chernobyl Nuclear Accident , Neoplasms, Radiation-Induced/metabolism , Oncogene Proteins, Fusion/metabolism , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins c-ret/physiology , Thyroid Neoplasms/physiopathology , Thyroid Nodule/physiopathology , Adult , Dose-Response Relationship, Radiation , Humans , Pilot Projects , Proto-Oncogene Proteins c-ret/metabolism , Ukraine
2.
Radiat Res ; 166(3): 519-31, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16953671

ABSTRACT

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.


Subject(s)
Chernobyl Nuclear Accident , Chromosome Mapping/methods , DNA, Neoplasm/genetics , Gene Dosage/genetics , Neoplasms, Radiation-Induced/genetics , Oligonucleotide Array Sequence Analysis/methods , Thyroid Neoplasms/genetics , Adolescent , Adult , Child , Child, Preschool , DNA Mutational Analysis/methods , Female , Humans , In Situ Hybridization, Fluorescence/methods , Infant , Male , Mutation , Power Plants , Prevalence , Radioactive Hazard Release , Sequence Alignment/methods , Sequence Analysis, DNA/methods , Ukraine
3.
J Natl Cancer Inst ; 97(10): 724-32, 2005 May 18.
Article in English | MEDLINE | ID: mdl-15900042

ABSTRACT

BACKGROUND: After the Chernobyl nuclear power plant accident in April 1986, a large increase in the incidence of childhood thyroid cancer was reported in contaminated areas. Most of the radiation exposure to the thyroid was from iodine isotopes, especially 131I. We carried out a population-based case-control study of thyroid cancer in Belarus and the Russian Federation to evaluate the risk of thyroid cancer after exposure to radioactive iodine in childhood and to investigate environmental and host factors that may modify this risk. METHODS: We studied 276 case patients with thyroid cancer through 1998 and 1300 matched control subjects, all aged younger than 15 years at the time of the accident. Individual doses were estimated for each subject based on their whereabouts and dietary habits at the time of the accident and in following days, weeks, and years; their likely stable iodine status at the time of the accident was also evaluated. Data were analyzed by conditional logistic regression using several different models. All statistical tests were two-sided. RESULTS: A strong dose-response relationship was observed between radiation dose to the thyroid received in childhood and thyroid cancer risk (P<.001). For a dose of 1 Gy, the estimated odds ratio of thyroid cancer varied from 5.5 (95% confidence interval [CI] = 3.1 to 9.5) to 8.4 (95% CI = 4.1 to 17.3), depending on the risk model. A linear dose-response relationship was observed up to 1.5-2 Gy. The risk of radiation-related thyroid cancer was three times higher in iodine-deficient areas (relative risk [RR]= 3.2, 95% CI = 1.9 to 5.5) than elsewhere. Administration of potassium iodide as a dietary supplement reduced this risk of radiation-related thyroid cancer by a factor of 3 (RR = 0.34, 95% CI = 0.1 to 0.9, for consumption of potassium iodide versus no consumption). CONCLUSION: Exposure to (131)I in childhood is associated with an increased risk of thyroid cancer. Both iodine deficiency and iodine supplementation appear to modify this risk. These results have important public health implications: stable iodine supplementation in iodine-deficient populations may substantially reduce the risk of thyroid cancer related to radioactive iodines in case of exposure to radioactive iodines in childhood that may occur after radiation accidents or during medical diagnostic and therapeutic procedures.


Subject(s)
Iodine Radioisotopes/adverse effects , Iodine/deficiency , Neoplasms, Radiation-Induced/etiology , Thyroid Gland/radiation effects , Thyroid Neoplasms/etiology , Adolescent , Adult , Case-Control Studies , Chernobyl Nuclear Accident , Child , Child, Preschool , Dose-Response Relationship, Radiation , Female , Humans , Incidence , Linear Models , Male , Middle Aged , Neoplasms, Radiation-Induced/epidemiology , Neoplasms, Radiation-Induced/prevention & control , Odds Ratio , Potassium Iodide/administration & dosage , Republic of Belarus/epidemiology , Risk Assessment , Russia/epidemiology , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/prevention & control
4.
Health Phys ; 88(1): 16-22, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15596986

ABSTRACT

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.


Subject(s)
Chernobyl Nuclear Accident , Thyroid Diseases/etiology , Thyroid Gland/radiation effects , Child , Child, Preschool , Dose-Response Relationship, Radiation , Female , Humans , Infant , Infant, Newborn , Male , Odds Ratio , Risk Assessment , Russia
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