Elucidation of genomic abnormalities in normal esophageal epithelium associated with radiation therapy and chemotherapy

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21574
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Kyoto University
• Principal Investigator: Yokoyama Akira 京都大学, 医学研究科, 助教 (20515514)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 食道がん / フィールドがん化 / 放射線療法 / 飲酒 / 喫煙 / ゲノム異常

Outline of Final Research Achievements

The purpose of this study was to elucidate the genomic abnormalities that accumulate in normal esophageal epithelium after radiation therapy. We performed multiple sampling of 6 sites from non-tumor areas within radiation therapy and 3 sites outside radiation therapy. Despite the presence of driver mutations outside of radiation therapy, we observed a phenomenon of disappearance of driver mutations in the mucosa within irradiation. 28 samples of esophageal mucosa within radiation therapy in 7 cases were used for a reproducibility cohort, but 82% (23/28) had driver mutations and were not reproducible. Therefore, we hypothesized that under certain conditions, esophageal drivers would disappear, but we were unable to find such conditions.

Free Research Field

ゲノム研究

Academic Significance and Societal Importance of the Research Achievements

食道がんは、フィールドがん化を呈するがんであり、飲酒・喫煙といったリスク因子の長期的な暴露により、食道全体ががんのリスクが高いため、一度治癒しても高い異時性多発がんの発症が報告されている。食道粘膜に対する放射線療法の効果は、このような異時性多発を減少させると考えられるプラスの面と、2次発がんのマイナス面と両面が有するが、食道粘膜にどのようなゲノム異常が生じるのか、その機序を理解することは、極めて重要である。今回は、全面的な解明には至らなかった。ドライバー変異がどのような症例に消失するのか、更に検討が必要である。