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      Effects of the Chernobyl Disaster on Thyroid Cancer Incidence in Turkey after 22 Years

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          Abstract

          Background. Separate studies involving people who survived atomic bombs have shown that the risk for cancer remains high after 40 years, compared with the risk in the general population. An elevated risk may also remain in regions of Turkey near the Chernobyl disaster. Patients and Methods. A multidisciplinary study conducted in 2008, 22 years after the Chernobyl disaster, examined the thyroid cancer incidence in Rize, a province of Turkey located on the shore of the middle Black Sea. Approximately 100,000 people were screened, and a fine-needle aspiration biopsy was performed in 89 patients. Results. Based on postoperative histopathological examinations, thyroid cancer was diagnosed in six of the 100,000 people screened. Conclusion. Given a thyroid cancer frequency of approximately 8 in 100,000 in the Turkish population, according to the Turkish Cancer Research Association, the rate in Rize reflects no increase in the thyroid cancer incidence 22 years after the Chernobyl disaster.

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          Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies.

          Marc Schneider, J Lubin, L Pottern … (1995)
          The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (> 10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 10(4) PY Gy (EAR/10(4) PY Gy) was 4.4 (95% CI = 1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P = 0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. Based on limited data, there was a suggestion that spreading dose over time (from a few days to > 1 year) may lower risk, possibly due to the opportunity for cellular repair mechanisms to operate. The thyroid gland in children has one of the highest risk coefficients of any organ and is the only tissue with convincing evidence for risk about 1.10 Gy.
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            RET/PTC rearrangements preferentially occurred in papillary thyroid cancer among atomic bomb survivors exposed to high radiation dose.

            R Ito, Midori Soda, Wataru Yasui … (2008)
            A major early event in papillary thyroid carcinogenesis is constitutive activation of the mitogen-activated protein kinase signaling pathway caused by alterations of a single gene, typically rearrangements of the RET and NTRK1 genes or point mutations in the BRAF and RAS genes. In childhood papillary thyroid cancer, regardless of history of radiation exposure, RET/PTC rearrangements are a major event. Conversely, in adult-onset papillary thyroid cancer among the general population, the most common molecular event is BRAF(V600E) point mutation, not RET/PTC rearrangements. To clarify which gene alteration, chromosome aberration, or point mutation preferentially occurs in radiation-associated adult-onset papillary thyroid cancer, we have performed molecular analyses on RET/PTC rearrangements and BRAF(V600E) mutation in 71 papillary thyroid cancer cases among atomic bomb survivors (including 21 cases not exposed to atomic bomb radiation), in relation to radiation dose as well as time elapsed since atomic bomb radiation exposure. RET/PTC rearrangements showed significantly increased frequency with increased radiation dose (P(trend) = 0.002). In contrast, BRAF(V600E) mutation was less frequent in cases exposed to higher radiation dose (P(trend) < 0.001). Papillary thyroid cancer subjects harboring RET/PTC rearrangements developed this cancer earlier than did cases with BRAF(V600E) mutation (P = 0.03). These findings were confirmed by multivariate logistic regression analysis. These results suggest that RET/PTC rearrangements play an important role in radiation-associated thyroid carcinogenesis.
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              Oncogenic rearrangements of the RET proto-oncogene in papillary thyroid carcinomas from children exposed to the Chernobyl nuclear accident.

              Sonia Greco, L Fugazzola, T Vorontsova … (1995)
              Since the Chernobyl nuclear reactor accident, a striking increase of thyroid carcinoma has been reported in children exposed to radiation in Belarus. Because of its unprecedented scale and its emotional implications, this finding has raised concern and called the attention of the scientific community to this major health problem. Although epidemiologically documented, a direct correlation between thyroid cancer and radiation exposure has not been definitely proven at the molecular level. On the assumption that ionizing radiation could cause specific and common cancer-associated genetic lesions, an analysis of oncogene activation and/or tumor suppressor gene inactivation would help to define radiation-induced thyroid carcinomas. Therefore, we have analyzed by different molecular approaches, including Southern blotting, DNA transfection assay on NIH-3T3 cells, and reverse transcription-PCR analysis, six papillary carcinomas from children living in the region of Belarus at the time of the Chernobyl nuclear accident to identify tumor-specific gene rearrangements of the proto-oncogenes RET and TRK, previously found activated in a tumor type-specific manner in papillary thyroid carcinoma. Using Southern blot analysis in four cases, we could detect specific rearranged bands indicating an oncogenic activation of RET that in three cases resulted in rearranged sequences provided by the same activating gene. Moreover, the DNA of the last three cases showed a biological activity in transforming NIH-3T3 cells after the DNA-mediated transfection assay, and the respective NIH-3T3 transfectants were found to express the oncogenic fusion transcripts. These results support the possibility that RET oncogenic activation could represent a major genetic lesion associated with thyroid carcinoma in children exposed to the Chernobyl nuclear accident.
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                Author and article information

                Journal
                Journal ID (nlm-ta): ISRN Surg
                Journal ID (publisher-id): SURGERY
                Title: ISRN Surgery
                Publisher: International Scholarly Research Network
                ISSN (Print): 2090-5785
                ISSN (Electronic): 2090-5793
                Publication date (Print): 2011
                Publication date (Electronic): 15 December 2011
                Volume: 2011
                Electronic Location Identifier: 257943
                Affiliations
                1Department of General Surgery, Large City Municipal Hospital, Ankara, Turkey
                2Department of Surgical Oncology, Ankara University School of Medicine, Turkey
                Author notes

                Academic Editors: D. A. Linos and V. Vecsei

                Article
                DOI: 10.5402/2011/257943
                PMC ID: 3246767
                PubMed ID: 22229102
                SO-VID: be910493-e7a6-4b3f-b2d9-1b5a02a67e7e
                Copyright © Copyright © 2011 Hasan Acar et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 20 October 2011
                Date accepted : 13 November 2011
                Categories
                Subject: Clinical Study

                ScienceOpen disciplines: Surgery
                Data availability:
                ScienceOpen disciplines: Surgery

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