Local differences in juvenile development of hepatocellular carcinoma in multi-racial Myanmar; focusing on the effect of iron and arsenic

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05813
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Nagasaki University
• Principal Investigator: KOJI Takehiko 長崎大学, 医歯薬学総合研究科(医学系), 教授 (30170179)
• Co-Investigator(Kenkyū-buntansha): 柴田 恭明 長崎大学, 医歯薬学総合研究科(医学系), 講師 (80253673) ; 遠藤 大輔 長崎大学, 医歯薬学総合研究科(医学系), 助教 (90516288) ; 穐山 直太郎 東京慈恵会医科大学, 医学部, 助教 (90554238)
• Research Collaborator: Kyaw Soe ; Kyaw Myat Phone ; Kyaw Zin Thant
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 肝癌 / 若年発症 / 鉄過剰摂取 / ヒ素 / 組織化学的解析 / Bcl9 / 居住地域性 / ミャンマー

Outline of Final Research Achievements

We have attempted to clarify the cause of juvenile development of hepatocellular carcinoma (HCC) in Myanmar. Our previous study revealed that iron overload could be one possible reason. Since now arsenic contaminated to water is known to be a big risk for cancers in South-Asian countries, we examined HCC specimens from various races living in different locations for the exposure to iron and arsenic. When 56 HCC tissues were analyzed for the markers of iron deposition and arsenic exposure, we found a significant variation in Prussian blue staining and 5-hydroxymethylcytosine level in DNA, indicating those specimens were more or less exposed to these toxic metals. Moreover, we found that Bcl9, which regulates the function of β-catenin, was lost in the cytoplasm of juvenile HCC. These results indicate that our future approach focusing on Bcl9 as a target of iron and arsenic toxicity will be useful to clarify the influences of these toxic metals on the juvenile development of HCC.

Free Research Field

分子解剖学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、今後更に民族間での若年性肝癌発症の差異を病理検体に基づき解析することにより、地域的な鉄及びヒ素の影響を明らかにでき、ひいてはその除去による発症リスクの除去を可能とすることを示している。また民族間での生活環境の違いによるこれら毒性物質の無毒化につながる伝統食の発掘への期待も膨らむ。特に今後の検討に於いて、若年性肝癌発症に関連する具体的な解析対象分子Bcl9を同定できたこともこれら毒性物質の作用機構を解明する上で大きな貢献と思われる。