Identification for radiation signature of cancer risk in irradiated thyroid

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08714
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Nagasaki University
• Principal Investigator: NAKASHIMA Masahiro 長崎大学, 原爆後障害医療研究所, 教授 (50284683)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 放射線被ばく / 発がん / 甲状腺 / 分子病理学 / バイオマーカー

Outline of Final Research Achievements

This study aimed to comprehensively examine the expression profile of genes altering in thyroid after irradiation (IR) by rat model and to identify biomarker in irradiated (IR) thyroid to estimate the cancer risk of individuals exposed to IR. Expression profile of mRNA in thyroid after IR were assessed by microarray technique, expression level of candidate for biomarker was quantitatively confirmed by digital PCR, and their usefulness as a biomarker was finally validated by a blinded experiment. In results, it was indicated that expression level of several molecules was abnormally altered in IR thyroid at precancerous stage. In particular, the level of CDKN1a expression was significantly increased in IR thyroid, and adopting 11.7-fold increase as a cutoff value to distinguish IR from non-IR, the sensitivity and specificity values were 60% and 100%, respectively. Thus, analysis for expression of these candidates may provide a biological evidence for IR effect in respective thyroids.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

被爆者疫学研究では甲状腺がんを始めとする人体における発がん影響が明らかにされていて、福島原発事故後の被曝健康影響の議論がなされてきた。疫学的データでは集団を対象とした被曝影響のリスク比として表現され、個人への放射線影響の評価は曖昧となるため、生物学的エビデンスを基盤とする放射線影響リスク評価の方法論の確立が喫緊の課題となる。本研究では、遺伝子発現の網羅的解析により、被曝甲状腺では前がん状態から分子異常が亢進していて、発がんリスクを反映することを初めて実証した。ラットモデルではCDKN1aが発がんリスク予測のバイオマーカーとして有用で、本法はヒトでのリスク評価への応用に期待できる。