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      Re: Thyroid Cancer Among Young People in Fukushima

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          Abstract

          To the Editor: Dr. Tsuda and colleagues 1 analyzed statistical reports of the Fukushima Health Management Survey published by the Fukushima prefectural government, and obtained markedly higher incidence rates of thyroid cancer in Fukushima Prefecture compared with the rate for all of Japan. Regrettably, their analysis has a serious methodological error regarding the prevalence pool with the 4-year duration. 1 They assumed a steady prevalence pool 2 of thyroid cancer cases detected by screening in Fukushima with using the definition of the “latent duration,” which is the time period from the date when a case of thyroid cancer became detectable by screening and cytology (“detectable by screening” hereafter) to the date when the thyroid cancer could be diagnosed in a clinical setting without screening or the date of operation (“detectable clinically”), using the duration of 4 years as the maximum length between the nuclear accident and the cancer detection. This assumption implies that the cancer in all cases became detectable by screening at or after the nuclear accident, and that all of these cancers progressed enough to be detected clinically within 4 years. However, both of them are unreasonable. They ignored two important possibilities: (1) the date at which a patient’s cancer becomes detectable by screening (which is usually unknown) might have preceded the nuclear accident, and (2) the slow growing nature of thyroid cancer 3 might cause many slowly progressing cases to remain in the pool. That is, the equilibrium of the pool within 4 years does not hold anymore. Thus, their incidence rate of the clinically detected cancer in Fukushima as the numerator of the paper’s incidence rate ratio—which is the essential index in the paper—is severely overestimated. The Fukushima Health Management Survey was commissioned by Fukushima Prefecture and has been conducted by the Radiation Medical Science Center for the Fukushima Health Management Survey at Fukushima Medical University since June 2011. With the efforts of over one hundred of the Center’s personnel, the results of the survey have become freely available on our website (http://fmu-global.jp) to ensure attention and transparency and to enable further examination of these findings. As Professor Scott Davis noted regarding the screening for thyroid cancer after the Fukushima accident, 4 “it should be of no surprise that a number of study designs and approaches have been tried, largely driven by the data available.” For the analyses, special attention should always be placed on the inherent limitations of the study. Hideto Takahashi Tetsuya Ohira Seiji Yasumura Kenneth E. Nollet Akira Ohtsuru Koichi Tanigawa Masafumi Abe Hitoshi Ohto Radiation Medical Science Center for the Fukushima Health Management SurveyFukushima Medical UniversityFukushima, Japanhtaka@fmu.ac.jp

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          Thyroid Growth and Cancer

          It is proposed that most papillary thyroid cancers originate in infancy and childhood, based on the early rise in sporadic thyroid carcinoma incidence, the pattern of radiation-induced risk (highest in those exposed as infants), and the high prevalence of sporadic papillary thyroid cancers in children and adolescents (ultrasound screening after the Fukushima accident). The early origin can be linked to the growth pattern of follicular cells, with a high mitotic rate in infancy falling to very low replacement levels in adult life. The cell of origin of thyroid cancers, the differentiated follicular cell, has a limited growth potential. Unlike cancers originating in stem cells, loss of the usually tight link between differentiation and replicative senescence is required for immortalisation. It is suggested that this loss distinguishes larger clinically significant papillary thyroid cancers from micro-papillary thyroid cancers of little clinical significance. Papillary carcinogenesis can then be divided into 3 stages: (1) initiation, the first mutation in the carcinogenic cascade, for radiation-induced papillary thyroid cancers usually a RET rearrangement, (2) progression, acquisition of the additional mutations needed for low-grade malignancy, and (3) escape, further mutations giving immortality and a higher net growth rate. Most papillary thyroid cancers will not have achieved full immortality by adulthood, and remain as so-called micro-carcinomas with a very low growth rate. The use of the term ‘cancer' to describe micro-papillary thyroid cancers in older patients encourages overtreatment and alarms patients. Invasive papillary thyroid tumours show a spectrum of malignancy, which at its lowest poses no threat to life. The treatment protocols and nomenclature for small papillary carcinomas need to be reconsidered in the light of the new evidence available, the continuing discovery of smaller lesions, and the model of thyroid carcinogenesis proposed.
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            Commentary: screening for thyroid cancer after the Fukushima disaster: what do we learn from such an effort?

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              Measures of effect and measures of association.

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                Author and article information

                Journal
                Epidemiology
                Epidemiology
                EDE
                Epidemiology (Cambridge, Mass.)
                Lippincott Williams & Wilkins
                1044-3983
                1531-5487
                May 2016
                01 April 2016
                : 27
                : 3
                : e21
                Affiliations
                Radiation Medical Science Center for the Fukushima Health Management Survey, Fukushima Medical University, Fukushima, Japan, htaka@ 123456fmu.ac.jp
                Article
                00036
                10.1097/EDE.0000000000000467
                4820659
                26844411
                84b3dd9d-c598-47fc-96c0-402594309440
                Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

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