カテゴリー「thyroid cancer」
Title: RET/PTC and PAX8/PPARγ chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with iodine-131 radiation dose and other characteristics.
Author: Leeman-Neill RJ, Brenner AV, Little MP, Bogdanova TI, Hatch M, Zurnadzy LY, Mabuchi K, Tronko MD, Nikiforov YE.
Reference: Cancer. 2013 Feb 21.
doi: 10.1002/cncr.27893.
Keywords: RET/PTC, chromosomal rearrangements, PAX8/PPARγ, iodine-131
Abstract: These results provide the first demonstration of PAX8/PPARγ rearrangements in post-Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with (131) I dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and (131) I exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients. Cancer 2013;. © 2013 American Cancer Society.
URL: http://www.ncbi.nlm.nih.gov/pubmed/23436219
Title: Recent trends in the incidence, geographical distribution, and survival from thyroid cancer in Wales: 1985-2010.
Author: Amphlett B, Lawson Z, Abdulrahman GO, White C, Bailey R, Premawardhana L, Okosieme OE.
Reference: Thyroid. 2013 Mar 14. [Epub ahead of print]
Keywords:
Abstract: Abstract Background Previous studies of thyroid cancer incidence in Wales have given varying results with suggestions of an excess of cases in geographic areas that were previously exposed to the radioactive fallout from the 1986 Chernobyl nuclear reactor incident. Our objective in this study was to provide an up to date comprehensive analysis of time trends in the incidence, geographical distribution, and survival from thyroid cancer in Wales. Methods We identified thyroid cancer cases, registered from 1985 through 2010 in the Welsh Cancer Intelligence and Surveillance Unit (WCISU). Age standardised rates were determined from the European standard population. A Poisson regression model was fitted to assess temporal trends and rate ratios (RR) and 95% confidence intervals (CI) were determined and compared across consecutive time periods: 1985-1997 and 1998-2010. Standardised incidence ratios were calculated for each of the 22 local authority areas. Relative survival and Kaplan Meier curves were computed to analyse all cause and thyroid cancer-specific survival. Results A total of 1747 thyroid cancer cases were registered from 1985-2010. Age standardised incidence rates were 2.8 and 1.2 per 100,000 population per year for females and males, respectively. Incidence rates increased with time (rate ratio 1.3, 95% CI 1.2-1.5, p<0.001, 1998-2010 vs.1985-1997). The incidence of papillary cancer increased progressively over the study period (RR 2.22, 95% CI 1.91-2.57, p<0.001; 1998-2010 vs.1985-1997), while rates for other (non-papillary) histological subtypes remained static (RR 0.95, 95% CI 0.84-1.08, p=0.45; 1998-2010 vs.1985-1997). We identified two geographical areas of increased incidence but the spatial distribution of cases was inconsistent with exposure to radioactive fallout. Five-year relative survival from all-cause mortality improved from 74.2 (95% CI 66.8-80.1) in 1985-1989, to 82.6 (95% CI 77.1-86.9) in 2000-2004 but remained poor for patients >65 years (p<0.001, >65 yrs vs. 15-64 years) and patients with anaplastic thyroid cancer (p<0.001, anaplastic vs. other histological varieties). Conclusions The incidence of thyroid cancer has increased in Wales, predominantly due to an increase in papillary cancers. The current geographical distribution of cases does not support a radiation effect in the region. Survival has remained poor for patients aged >65 years and those with anaplastic carcinoma.
URL: http://www.ncbi.nlm.nih.gov/pubmed/23488941
Title: Chernobyl cleanup workers from Estonia: follow-up for cancer incidence and mortality.
Author: Rahu K, Auvinen A, Hakulinen T, Tekkel M, Inskip PD, Bromet EJ, Boice Jr JD, Rahu M.
Reference: J Radiol Prot. 2013 Mar 27;33(2):395-411. [Epub ahead of print]
doi:
Keywords: incidence, mortality, cleanup workers
Abstract: This study examined cancer incidence (1986-2008) and mortality (1986-2011) among the Estonian Chernobyl cleanup workers in comparison with the Estonian male population. The cohort of 4810 men was followed through nationwide population, mortality and cancer registries. Cancer and death risks were measured by standardised incidence ratio (SIR) and standardised mortality ratio (SMR), respectively. Poisson regression was used to analyse the effects of year of arrival, duration of stay and time since return on cancer and death risks. The SIR for all cancers was 1.06 with 95% confidence interval 0.93-1.20 (232 cases). Elevated risks were found for cancers of the pharynx, the oesophagus and the joint category of alcohol-related sites. No clear evidence of an increased risk of thyroid cancer, leukaemia or radiation-related cancer sites combined was apparent. The SMR for all causes of death was 1.02 with 95% confidence interval 0.96-1.08 (1018 deaths). Excess mortality was observed for mouth and pharynx cancer, alcohol-related cancer sites together and suicide. Duration of stay rather than year of arrival was associated with increased mortality. Twenty-six years of follow-up of this cohort indicates no definite health effects attributable to radiation, but the elevated suicide risk has persisted.
URL: http://www.ncbi.nlm.nih.gov/pubmed/23532116
Title: Chernobyl-related thyroid cancer: what evidence for role of short-lived iodines?
Author: J P Bleuer, Y I Averkin, and T Abelin
Reference: Environ Health Perspect. 1997 December; 105(Suppl 6): 1483–1486.
doi:
Keywords:
Abstract: Over 500 cases of thyroid cancer were diagnosed in Belarus between 1986 and 1995 among persons exposed as children (under 15 years of age) to radioactive contamination from the Chernobyl nuclear accident. There is little doubt that radioactive iodine isotopes emitted during the nuclear explosion and subsequent fire were instrumental in causing malignancy in this particular organ. Comparison of the observed geographic distribution of Chernobyl-associated thyroid cancer incidence rates by districts with contamination maps of radioactive fallout shows a better fit for estimated 131I contamination than for 137Cs. Because 131I used for medical purposes had not been considered carcinogenic in humans in the past, and in view of the unusually short latency period between exposure and clinical manifestation of cancer, it is suspected that not only 131I but also energy-rich shorter-lived radioiodines may have played a role in post-Chernobyl thyroid carcinogenesis. Measurements of iodine isotopes are not available, but reconstruction of geographic distributions and estimations of radioactive fallout based on meteorological observations immediately following the accident could provide a basis for comparison with the distribution of thyroid cancer cases. In this paper, data from the Epidemiological Cancer Register for Belarus will be used to show geographic and time trends of thyroid cancer incidence rates in the period from 1986 to 1995 among persons who were exposed as children, and these will be compared with the estimated contamination by radioiodines. Tentative conclusions are drawn from the available evidence and further research requirements discussed.
URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1469926/
Title: Occult thyroid carcinomas in the region of Minsk, Belarus. An autopsy study of 215 patients.
Author: Furmanchuk AW, Roussak N, Ruchti C. Research Institute for Oncology and Medical Radiology, Minsk, Republic of Belarus.
Reference: Histopathology. 1993 Oct;23(4):319-25.
doi:
Keywords:
Abstract: Thyroid glands from 215 patients, aged 19 to 88 years, without known thyroid disease, were serially sectioned at 2-3 mm intervals and microscopically examined for occult disease. Glands were normal in 32.5%, while nodules were observed in 60% and adenomas in 13%. Carcinomas were found in 20 cases (9.3%): occult papillary carcinomas in 19 (8.8%) and one medullary carcinoma. No carcinomas were found in the thyroids of 15 patients less than 40 years of age. There were no significant differences in frequency of occult carcinomas between female and male patients and, for patients over 40 years, with increasing age. Of the 19 papillary tumours more than one focus was found in six cases (a total of 28 foci). The diameter of 27 of these tumours was less than or equal to 5 mm (96.4%), with one exception (diameter 6.3 mm). These findings were compared with those obtained in 86 thyroid glands of children surgically resected for carcinomas between 1986 and 1991. Only 10 of these tumours (11.6%) were less than or equal to 1 cm. These tumours, however, were significantly larger than the occult papillary carcinomas and their morphological features were quite different. Our results are discussed with regard to the possible role of factors other than irradiation due to the nuclear accident at Chernobyl, and the observed sharp numerical increase of thyroid carcinomas in children of the Republic of Belarus after this event.
URL: http://www.ncbi.nlm.nih.gov/pubmed/8300067
Title: Childhood thyroid diseases around Chernobyl evaluated by ultrasound examination and fine needle aspiration cytology.
Author: Ito M, Yamashita S, Ashizawa K, Namba H, Hoshi M, Shibata Y, Sekine I, Nagataki S, Shigematsu I. Department of Pathology, Nagasaki University School of Medicine, Japan.
Reference: Thyroid. 1995 Oct;5(5):365-8.
doi:
Keywords:
Abstract: Screening by ultrasound examination and fine-needle aspiration cytological biopsy (FNA) was conducted in five regions in Belarus, Ukraine, and Russia to investigate the prevalence of childhood thyroid diseases around Chernobyl. Gomel, Zhitomir, Kiev, and the western area of Bryansk are the administrative regions where severe radioactive contamination occurred. The subjects from Mogilev, where contamination was relatively low, served as controls. Among 55,054 subjects (26,406 boys and 28,648 girls), the prevalence of ultrasonographic thyroid abnormalities such as nodule, cyst, and abnormal echogenity was significantly higher in the regions with severe contamination than in Mogilev. Of the 1,396 children showing echographic thyroid abnormalities 197 were selected for FNA, and a sample was successfully obtained for diagnosis from 171 (51 boys and 120 girls) of the 197 subjects. The aspirate was insufficient for diagnosis in the remaining 26 subjects. Thyroid cancer was encountered in four children (2.3%) from the contaminated regions, two children being from Gomel. The other thyroid diseases were follicular neoplasm, 6.4%; adenomatous goiter, 18.7%; chronic thyroiditis, 31.0%; and cyst, 24.0%, suggesting that a major cause of thyroid nodularity is nonneoplastic changes, mainly chronic thyroiditis and cysts. These results will serve as an important data base for further analyses and suggest that childhood thyroid diseases, including both neoplasms and immunological disorders, are consequences of radioactive fallout.
URL: http://www.ncbi.nlm.nih.gov/pubmed/8563473
Title: Pediatric thyroid cancer after the Chernobyl disaster. Pathomorphologic study of 84 cases (1991-1992) from the Republic of Belarus.
Author: Nikiforov Y, Gnepp DR.
Reference: Cancer. 1994 Jul 15;74(2):748-66.
doi:
Keywords:
Abstract: Post-Chernobyl pediatric thyroid carcinoma is characterized by a short latency, a higher proportion of tumors arising in young children, and an almost equal sex ratio. Microscopically, these tumors were usually aggressive, often demonstrating intraglandular tumor dissemination (92%), thyroid capsular and adjacent soft tissue invasion (89%), and cervical lymph node metastases (88%). Papillary carcinoma was diagnosed in 99% of cases, with an unusually high frequency of solid growth patterns. Morphologic changes in nonneoplastic thyroid tissue were present in 90% of the glands, and the most specific findings were vascular changes and perifollicular fibrosis.
URL: http://www.ncbi.nlm.nih.gov/pubmed/8033057
Title: Heterogeneity in the distribution of RET/PTC rearrangements within individual post-Chernobyl papillary thyroid carcinomas
Author: Unger, K., Zitzelsberger, H., Salvatore, G.*, Santoro, M.*, Bogdanova, T.*, Braselmann, H., Kastner, P.,Zurnadzhy, L.*, Tronko, N.*, Hutzler, P., Thomas, G.:. J.
Reference: Clin. Endocr. Metab. 89, 4272-4279 (2004)
Keywords:
Abstract: The nuclear disaster that occurred in Chernobyl in 1986 offered the unique opportunity to study the molecular genetics of one human tumor type, papillary carcinoma of the thyroid gland, associated with a specific etiology. We have analyzed RET rearrangements in post-Chernobyl papillary thyroid carcinomas (n = 29), follicular thyroid adenomas (n = 2), and follicular thyroid carcinoma (n = 1) by interphase fluorescence in situ hybridization (FISH) analysis on paraffin-embedded tissue sections. Paraffin sections were microdissected before use to ensure that only tumor was present. Cell nuclei were scored for the presence of a split FISH signal (separated red and green signal) in addition to an overlapping signal. Only cells with either two overlapping signals or one split and one overlapping signal were counted to ensure that only complete cell nuclei had been scored. In total, 23 of 32 cases (72%) showed RET rearrangements diagnosed by FISH interphase analysis. In all cases, the tumors were composed of a mixture of cells with and without ret rearrangement on FISH. In some cases, this distribution was clearly nonrandom because clustering of rearranged cells was detected within the same tumor nodule. Accordingly, only 31% of the cases positive for rearrangement on FISH also scored positive using RT-PCR. These findings suggest that because RET/PTC rearrangements are not present in a majority of tumor cells, either a fraction of post-Chernobyl papillary thyroid tumors are of multiclonal origin, or ret rearrangement is a later, subclonal event.
URL: http://www.ncbi.nlm.nih.gov/pubmed/15356021
Title: Influence of radionuclides distributed in the whole body on the thyroid dose estimates obtained from direct thyroid measurements made in Belarus after the Chernobyl accident.
Author: Ulanovsky, A., Drozdovitch, V.*, Bouville, A.*:
Reference: Radiat. Prot. Dosim. 112, 405-418 (2004)
Keywords:
Abstract: Thyroid dose reconstruction is most accurate when using the results of direct thyroid measurements, in which gamma radiation emitted by radionuclides present in the thyroid and in the remainder of the body is recorded by means of a radiation detector positioned against the neck. A large number of such measurements were performed in Belarus in May-June 1986. Owing to the short half-life of 131I and to the intake and accumulation of caesium radioisotopes (mainly 134Cs and 137Cs) in the body, the thyroid doses derived from thyroid measurements made after the beginning of June 1986 have so far been often considered to be unreliable. To evaluate the influence of the caesium radioisotopes to the signal recorded by an instrument performing measurement of 131I activity in the thyroid, a Monte Carlo method was used to calculate the calibration factors of that instrument. These calculations were made for males of six reference ages: newborn, 1, 5, 10 and 15 years old, and adult. The calibration factors were combined with estimated time-dependent intake functions for 131I and caesium radioisotopes. The fractions of the instrument indications that were due to 131I in thyroid were thus estimated as a function of the age of the subject that was measured and of the time elapsed since the accident. Using this information when processing the thyroid measurements made in May 1986 would improve the accuracy of the thyroid dose estimates, and may make it possible to use a larger proportion of the thyroid measurements made in June 1986.
URL:http://www.ncbi.nlm.nih.gov/pubmed/15494363
Title: : Chromosomal imbalances in post-Chernobyl thyroid tumors.
Author: Richter, H., Braselmann, H., Hieber, L., Thomas, G.*, Bogdanova, T.*
Reference: Thyroid 14, 1061-1064 (2004)
Keywords: childhood thyroid tumors
Abstract: Tissue samples from 60 post-Chernobyl childhood thyroid tumors have been investigated. We used comparative genomic hybridization (CGH) to detect chromosomal gains and losses within the tumor DNA. This is the first CGH study on childhood thyroid tumors. The post-Chernobyl tumors showed chromosomal imbalances in 30% of tumors. The most frequent DNA copy number changes in post-Chernobyl tumors involved chromosomes 2, 7q11.2-21, 13q21-22, 21 (DNA gains), and chromosomes 16p/q, 20q, 22q (DNA losses). Some of these specific alterations detected in post-Chernobyl thyroid tumors (deletions on chromosomes 16p/q and 22q) have previously been reported in thyroid tumors as associated with an aggressive biologic behavior and may therefore also account for the more aggressive phenotype of papillary thyroid carcinoma (PTC) found in post- Chernobyl tumors. Eighteen percent of post-Chernobyl PTC that exhibit RET rearrangements also showed chromosomal imbalances indicating that either additional genetic events are involved in this subset of tumors, or that intratumoral genetic heterogeneity exists in these tumors, suggesting a oligoclonal pattern to tumor development.
URL: http://www.ncbi.nlm.nih.gov/pubmed/15650359
