Stratification of East Asian H.pylori strains to construct the basis for selective H.pylori eradication therapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16707
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Chiba University
• Principal Investigator: Fukuyo Masaki 千葉大学, 大学院医学研究院, 助教 (40639085)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ピロリ菌 / 胃癌 / DNAメチル化 / 発癌 / 制限酵素

Outline of Final Research Achievements

H. pylori is a gastric carcinogen. CagA protein is known as a carcinogen, however, it is not clear how non-cancer-causing cagA and cagA- H. pylori strains cause genomic mutations and epigenomic abnormalities in the host cell, leading to carcinogenesis. H. pylori infection increasing the gastric cancer risk, however it also suppressing esophagogastric junction cancer. It is necessary to classify H. pylori that should be eradicated or should not be eradicated.
In this study, in order to create a basis for the selective eradication treatment of high risk H. pylori, the characteristics of H. pylori to be eradicated by stratification of 110 East-Asian H. pylori strains were elucidated by human genome data and H. pylori genome/DNA methylation data. Restriction glycosylase in H. pylori was indicated as gastric cancer carcinogen.

Free Research Field

微生物発癌

Academic Significance and Societal Importance of the Research Achievements

胃がんは本邦において毎年10万人以上が羅漢し，約5万人が命を落とす主要な疾患の一つである．胃癌発症の主因はピロリ菌であるが，その発癌の仕組みはcagA等の一部の例外を除いてまだ不明である．ここに私達はピロリ菌多数株のゲノム・メチローム比較と，ヒト癌変異解析からピロリ菌の持つ塩基切り出し型制限酵素がヒト胃上皮細胞に変異を誘発し胃癌を引き起こしているという仮説を提唱した．
また，今回胃癌変異源候補として見出したHpPabIは選択的ピロリ菌除菌治療の指標となり得る．