ピロリ菌除菌者での初発胃がんリスク診断に成功~胃の細胞に溜まったエピゲノム異常で正確にリスク判定できることを確認 実用化に向け検討を開始~

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2025-04-16 星薬科大学,国立がん研究センター

国立がん研究センターと星薬科大学の研究チームは、ピロリ菌除菌後の健康な人々において、胃粘膜組織のDNAメチル化異常を測定することで、初発胃がんリスクを精密に予測できることを多施設共同前向き研究により明らかにしました。この研究では、開放型胃粘膜萎縮を有する1,624名を対象に、RIMS1遺伝子のメチル化レベルを測定し、5年間追跡調査を実施。その結果、メチル化レベルが最も高い群は、最も低い群に比べて胃がん発生リスクが7.7倍高いことが判明しました。特に、メチル化レベルが25.7%を超えるとリスクが急増することから、超高リスク群の特定にも成功しました。この成果は、個別化された検診間隔の設定や、低リスク群の特定による検診負担の軽減に寄与すると期待されます。研究成果は、2025年4月16日に国際学術誌「Gut」に発表されました。

<関連情報>

DNAメチル化マーカーによるピロリ除菌後の原発性胃癌の精密リスク層別化:多施設前向き研究 Precision risk stratification of primary gastric cancer after eradication of H. pylori by a DNA methylation marker: a multicentre prospective study

Harumi Yamada,Hadrien Charvat,Takayuki Ando,Masahiro Maeda,Kazunari Murakami,Takao Maekita,Mitsushige Sugimoto,Takahisa Furuta,Mitsuru Kaise,Nobutake Yamamichi,Akiko Sasaki,Sohachi Nanjo,Nobuhiro Suzuki,Toshiro Sugiyama,Masaaki Kodama,Kazuhiro Mizukami,Masanori Ito,Takahiro Kotachi,Seiichiro Yamamoto,Toshikazu Ushijima
Gut  Published: April 15, 2025
DOI:https://doi.org/10.1136/gutjnl-2025-335039

ピロリ菌除菌者での初発胃がんリスク診断に成功~胃の細胞に溜まったエピゲノム異常で正確にリスク判定できることを確認 実用化に向け検討を開始~

Abstract

Background Precision cancer risk stratification for gastric cancer is urgently needed for the growing number of healthy people after Helicobacter pylori eradication. The epimutation burden in non-malignant tissues has been associated with cancer risk in multiple cross-sectional studies.

Objective To confirm the clinical usefulness of a DNA methylation marker for epimutation burden, and to identify a cut-off methylation level for a super-high-risk population.

Design Healthy people after H. pylori eradication with open-type atrophy were prospectively recruited. DNA methylation levels of a marker gene, RIMS1, were measured in biopsy specimens from gastric antrum and body. The primary endpoint was the incidence rate of gastric cancer in quartiles of the methylation levels.

Results 1624 participants had at least one endoscopic follow-up with a median follow-up of 4.05 years, and a primary gastric cancer developed in 27 participants. The highest quartile of RIMS1 methylation levels had a higher incidence rate (972.8 per 100 000 person-years) than the lowest quartile (127.1). Cox regression analysis revealed a univariate HR of 7.7 (95% CI 1.8–33.7) and an age- and sex-adjusted HR of 5.7 (95% CI 1.3–25.5). As a secondary objective, a cut-off methylation level of 25.7% (95% CI 1.7–7.7) was obtained to identify a population with a super-high risk based on the number needed to screen of 1000.

Conclusion A DNA methylation marker can risk-stratify healthy people after H. pylori eradication even though all of them have clinically high risk. Individuals with super-high risk will need more frequent gastric cancer screening than currently recommended.

Trial registration number UMIN-CTR000016894.

医療・健康
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