Identification of novel risk factors for gastric cancer development by analysis of antioxidant capacity, DNA repair capacity, and DNA mutation levels.

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K16722
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Juntendo University
• Principal Investigator: Ikuse Tamaki 順天堂大学, 医学部, 助教 (70750876)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: ヘリコバクター・ピロリ / 胃がん / 酸化ストレス / 抗酸化物質 / 塩基除去修復酵素

Outline of Final Research Achievements

To evaluate the resistance of the gastric mucosa to oxidative stress, a factor in the development of gastric cancer, and the effects of aging and H. pylori infection on this resistance, the antioxidant capacity and the ability to repair DNA damage caused by oxidative stress were analyzed using human gastric mucosa and compared among four groups: children and adults with H. pylori-infection and children and adults without H. pylori infection. The results showed that antioxidant capacity and DNA repair capacity decreased with age, and that H. pylori infection further decreased antioxidant capacity. This suggests that the increase in the risk of gastric cancer over time is due to a decrease in the expression of antioxidants and DNA repair capacity, and that H. pylori infection could increase the risk of gastric cancer not only by producing oxidative stress through inflammation, but also by further decreasing the expression of antioxidants.

Free Research Field

小児消化器学

Academic Significance and Societal Importance of the Research Achievements

加齢により胃がん発生リスクが増大することは知られているが、加齢がどのような発がん要因をもたらすのかは判明していない。本研究の成果は、加齢に伴い発がん主因の一つである酸化ストレスへの抵抗力が失われていくことを示している。ピロリ菌感染に伴う慢性胃炎とそれによる胃粘膜変化は胃がん発生を引き起こす最たるリスクファクターであるため、現在まで胃がん発生リスクはピロリ菌感染既往の有無と胃粘膜変化の程度から評価されてきたが、胃粘膜の抗酸化能やDNA修復能は胃がん発生リスクを評価する新規のバイオマーカーとなる可能性があり、これによってピロリ菌未感染者の胃がん発生リスクをも定量化されることが期待される。