Molecular mechanism for predisposition to develop oral cancer based on epigenome modification in utero

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K10052
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Kyushu University
• Principal Investigator: Kawakubo-Yasukochi Tomoyo (川久保友世) 九州大学, 歯学研究院, 准教授 (70507813)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: DOHaD / 口腔癌 / エピゲノム / 炎症 / 葉酸

Outline of Final Research Achievements

In this research, the effect of maternal folic acid intake in the gestational period on the carcinogenic susceptibility of the next generation was elucidated.
As a result of research, maternal folic acid shortage in pregnancy caused methylation abnormalities in the deubiquitinating enzyme gene(s) in the fetal, causing abnormal expression of the gene(s), and the epigenomic change lasts even after the offspring had matured. It was demonstrated that the sensitivity to induction of inflammation was increased, and its tendency was particularly remarkable in the squamous epithelial tissue. Furthermore, it was revealed that maternal folic acid shortage in pregnancy increases the carcinogenic susceptibility of offspring to oral squamous cell cancer. This suggests that proper maternal intake of folic acid contributes to the suppression of oral cancer carcinogenesis in the offspring.

Free Research Field

生化学、分子生物学、薬理学

Academic Significance and Societal Importance of the Research Achievements

こでまでに、がんにおけるエピゲノム制御については、詳細な検討がなされてきたが、母体(因)と仔 (果)の因果関係について総合的把握を行った研究は非常に少ない。本研究課題では、がんの発症素因として胎内の栄養状態によるエピゲノム変異（先天的環境要因）の提示を行った。口腔癌発症素因が、母体の妊娠期栄養状態によって胎内で既定されうることをその分子基盤を以て実証したことにより、栄養学を通して予防歯学の基盤確立に貢献した。また、現在まで環境素因が主な原因とされてきた口腔癌の病因論に一石を投じることになった。