Evidence map›Paper›PMID 25379950›Full record

ArticleGut2015

Demonstration of the usefulness of epigenetic cancer risk prediction by a multicentre prospective cohort study.

Kiyoshi Asada, Takeshi Nakajima, Taichi Shimazu, Nobutake Yamamichi, Takao Maekita, Chizu Yokoi, Ichiro Oda, Takayuki Ando, Takeichi Yoshida, Sohachi Nanjo and 4 more

Open access · hybridAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Gut, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 2 pooled it
5.3field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

94 citing papers in PubMed, 2 syntheses or guidelines pooled it, 177 citations in OpenAlex.

  1. Chemoprevention of gastric cancer development afterWorld journal of gastroenterology · 2020
    Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. DNA Methylation Predicts Progression of Human Gastric Lesions.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2015
    Trial
  6. Review
  7. Article
  8. Review
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  12. Concurrent hypermethylation of CpG islands and hypomethylation of CpG-poor regions are associated with gastric cancer risk after Helicobacter pylori eradication.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025
    Article
  13. Article
  14. Article
  15. Review
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34 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Kiyoshi AsadaDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
Takeshi NakajimaEndoscopy Division, National Cancer Center Hospital, Tokyo, Japan.
Taichi ShimazuEpidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
Nobutake YamamichiDepartment of Gastroenterology, University of Tokyo, Tokyo, Japan.
Takao MaekitaSecond Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
Chizu YokoiEndoscopy Division, National Cancer Center Hospital, Tokyo, Japan Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Tokyo, Japan.
Ichiro OdaEndoscopy Division, National Cancer Center Hospital, Tokyo, Japan.
Takayuki AndoDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
Takeichi YoshidaSecond Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
Sohachi NanjoDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
Mitsuhiro FujishiroDepartment of Gastroenterology, University of Tokyo, Tokyo, Japan.
Takuji GotodaEndoscopy Division, National Cancer Center Hospital, Tokyo, Japan Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan.
Masao IchinoseSecond Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
Toshikazu UshijimaDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
National Cancer Center Hospital East · JPWakayama Medical University · JPThe University of Tokyo · JPTokyo Medical University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEpigenetic alterations accumulate in normal-appearing tissues of patients with cancer, producing an epigenetic field defect. Cross-sectional studies show that the degree of the defect may be associated with risk in some types of cancer, especially cancers associated with chronic inflammation.

objectiveTo demonstrate, by a multicentre prospective cohort study, that the risk of metachronous gastric cancer after endoscopic resection (ER) can be predicted by assessment of the epigenetic field defect using methylation levels.

designPatients with early gastric cancer, aged 40-80 years, who planned to have, or had undergone, ER, were enrolled at least 6 months after Helicobacter pylori infection discontinued. Methylation levels of three preselected genes (miR-124a-3, EMX1 and NKX6-1) were measured by quantitative methylation-specific PCR. Patients were followed up annually by endoscopy, and the primary endpoint was defined as detection of a metachronous gastric cancer. Authentic metachronous gastric cancers were defined as cancers excluding those detected within 1 year after the enrolment.

resultsAmong 826 patients enrolled, 782 patients had at least one follow-up, with a median follow-up of 2.97 years. Authentic metachronous gastric cancers developed in 66 patients: 29, 16 and 21 patients at 1-2, 2-3 and ≥3 years after the enrolment, respectively. The highest quartile of the miR-124a-3 methylation level had a significant univariate HR (95% CI) (2.17 (1.07 to 4.41); p=0.032) and a multivariate-adjusted HR (2.30 (1.03 to 5.10); p=0.042) of developing authentic metachronous gastric cancers. Similar trends were seen for EMX1 and NKX6-1.

conclusionsAssessment of the degree of an epigenetic field defect is a promising cancer risk marker that takes account of life history.

Indexed as

DNA MethylationEpigenesis, GeneticAdultAgedAged, 80 and overEmpty Spiracles Homeobox ProteinsFemaleGenetic MarkersHomeodomain ProteinsHumansMaleMicroRNAsMiddle AgedNeoplasms, Second PrimaryPolymerase Chain ReactionProspective StudiesEmpty Spiracles Homeobox ProteinsGenetic MarkersHomeodomain ProteinsMicroRNAsMIRN124 microRNA, humanNKX6-1 protein, humanTranscription FactorsGASTRIC CANCERMETHYLATION

Identifiers

PMID25379950
PMCPMC4345890
OpenAlexW2102844953

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.