{
  "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.",
  "authors": [
    {
      "affiliations": [
        "Department of Epigenomics, Institute for Advanced Life Sciences, Hoshi University, Tokyo, Japan",
        "Department of Gastrointestinal Surgery, Kyoto University, Kyoto, Japan",
        "Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan"
      ],
      "name": "Harumi Yamada"
    },
    {
      "affiliations": [
        "Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan"
      ],
      "name": "Seiichiro Abe"
    },
    {
      "affiliations": [
        "Faculty of International Liberal Arts, Juntendo University, Tokyo, Japan",
        "Division of International Health Policy Research, Institute for Cancer Control, National Cancer Center, Tokyo, Japan"
      ],
      "name": "Hadrien Charvat"
    },
    {
      "affiliations": [
        "Third Department of Internal Medicine, University of Toyama, Toyama, Japan"
      ],
      "name": "Takayuki Ando"
    },
    {
      "affiliations": [
        "Department of Gastrointestinal Surgery, Kyoto University, Kyoto, Japan",
        "Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan"
      ],
      "name": "Masahiro Maeda"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan"
      ],
      "name": "Kazunari Murakami"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan"
      ],
      "name": "Shiro Oka"
    },
    {
      "affiliations": [
        "Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan"
      ],
      "name": "Takao Maekita"
    },
    {
      "affiliations": [
        "Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Shiga, Japan",
        "Division of Genome-Wide Infectious Microbiology, Research Center for GLOBAL and LOCAL Infectious Disease, Oita University, Oita, Japan"
      ],
      "name": "Mitsushige Sugimoto"
    },
    {
      "affiliations": [
        "Center for Clinical Research, Hamamatsu University School of Medicine, Shizuoka, Japan"
      ],
      "name": "Takahisa Furuta"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan"
      ],
      "name": "Mitsuru Kaise"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, The University of Tokyo, Graduate School of Medicine, Tokyo, Japan"
      ],
      "name": "Nobutake Yamamichi"
    },
    {
      "affiliations": [
        "Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan"
      ],
      "name": "Hiroyuki Takamaru"
    },
    {
      "affiliations": [
        "Gastroenterology Medicine Center, Shonan Kamakura General Hospital, Kanagawa, Japan"
      ],
      "name": "Akiko Sasaki"
    },
    {
      "affiliations": [
        "Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan"
      ],
      "name": "Ichiro Oda"
    },
    {
      "affiliations": [
        "Third Department of Internal Medicine, University of Toyama, Toyama, Japan"
      ],
      "name": "Sohachi Nanjo"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Joetsu General Hospital, Niigata, Japan"
      ],
      "name": "Nobuhiro Suzuki"
    },
    {
      "affiliations": [
        "Third Department of Internal Medicine, University of Toyama, Toyama, Japan",
        "Health Sciences University of Hokkaido, Hokkaido, Japan (Present adrress)"
      ],
      "name": "Toshiro Sugiyama"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan",
        "Department of Advanced Medical Sciences, Faculty of Medicine, Oita University, Oita, Japan"
      ],
      "name": "Masaaki Kodama"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan"
      ],
      "name": "Kazuhiro Mizukami"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan"
      ],
      "name": "Masanori Ito"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan"
      ],
      "name": "Takahiro Kotachi"
    },
    {
      "affiliations": [
        "Epidemiology and Prevention Group, Research Center for Cancer Prevention andScreening, National Cancer Center, Tokyo, Japan"
      ],
      "name": "Taichi Shimazu"
    },
    {
      "affiliations": [
        "Shizuoka Graduate University of Public Health, Shizuoka, Japan"
      ],
      "name": "Seiichiro Yamamoto"
    },
    {
      "affiliations": [
        "Department of Epigenomics, Institute for Advanced Life Sciences, Hoshi University, Tokyo, Japan",
        "Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan"
      ],
      "name": "Toshikazu Ushijima"
    }
  ],
  "title": "Precision risk stratification of primary gastric cancer after eradication of H. pylori by a DNA methylation marker: a multicentre prospective study",
  "uid": "46945a8f-9a56-5f2a-b6cf-29e1cd9cc6d3"
}