{
  "abstract": "Background Previous studies have suggested a possible association between Helicobacter pylori (H. pylori) infection and an increased risk of colorectal cancer (CRC).Objective We examined the associations of H. pylori infection and H. pylori treatment with incident CRC risk and evaluated whether these associations were modified by genetic susceptibility.Design This study was based on two randomised trial cohorts: the Shandong Intervention Trial (SIT; n=3365; 1995–2024) and the Mass Intervention Trial in Linqu, Shandong Province (MITS; n=180 284; 2011–2024). Within MITS, we further conducted a case-cohort study to assess CRC risk according to seropositivity for H. pylori virulence factors and host genetic predisposition.Results Compared with H. pylori-negative individuals, H. pylori-positive individuals who did not receive antibiotic treatment had a significantly higher risk of CRC (SIT: HR=2.96, 95% CI 1.30 to 6.71; MITS: HR=1.27, 95% CI 1.04 to 1.55). The increased risk was particularly evident among individuals seropositive for four H. pylori-specific antigens (CagA, HpaA, Omp and HP0305) and those at high genetic risk (top decile of the Polygenic Risk Score). In SIT, H. pylori treatment was associated with a significantly reduced CRC risk over 29.4 years of follow-up (HR=0.47, 95% CI 0.22 to 0.99), with a greater reduction observed among participants with successful eradication (HR=0.38, 95% CI 0.15 to 0.94). In MITS, no overall benefit was observed 13.8 years after treatment (HR=1.17, 95% CI 0.95 to 1.43). However, a protective effect was apparent among individuals at high genetic risk and among those seropositive for key H. pylori-specific antigens.Conclusion In post hoc observational analyses of two established trial cohorts, H. pylori infection was associated with an increased risk of CRC. H. pylori treatment reduced CRC risk in SIT, whereas in MITS, the benefit appeared to be limited to individuals at high genetic risk or those infected with specific virulence factor subtypes.",
  "authors": [
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Xuan Han"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Heng-Min Xu"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Zong-Chao Liu"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Lian Zhang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Zhi-Qiang Hu"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Wen-Jing Zhao"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Ji-Er Zhao"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Feng-Rui Zhu"
    },
    {
      "affiliations": [
        "Health Bureau of Linqu County, Weifang, China"
      ],
      "name": "Wei-dong Liu"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Jun-Ling Ma"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Yang Zhang"
    },
    {
      "affiliations": [
        "Health Bureau of Linqu County, Weifang, China"
      ],
      "name": "Jian-Xi Wang"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Lei Zhang"
    },
    {
      "affiliations": [
        "Health Bureau of Linqu County, Weifang, China"
      ],
      "name": "Lan-Fu Zhang"
    },
    {
      "affiliations": [
        "Health Bureau of Linqu County, Weifang, China"
      ],
      "name": "Ming Li"
    },
    {
      "affiliations": [
        "Health Bureau of Linqu County, Weifang, China"
      ],
      "name": "Le-Hua Wang"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Tong Zhou"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Wei-Xiang Guan"
    },
    {
      "affiliations": [
        "Institute for Medical Microbiology, Immunology and Hygiene, TUM School of Medicine and Health, Department Preclinical Medicine, Technical University of Munich, Munich, Germany"
      ],
      "name": "Raquel Mejías-Luque"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Wei-Cheng You"
    },
    {
      "affiliations": [
        "Institute for Medical Microbiology, Immunology and Hygiene, TUM School of Medicine and Health, Department Preclinical Medicine, Technical University of Munich, Munich, Germany"
      ],
      "name": "Markus Gerhard"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Kai-Feng Pan"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China"
      ],
      "name": "Wen-Qing Li"
    }
  ],
  "title": "Helicobacter pylori infection, treatment and colorectal cancer risk by genetic predisposition: evidence from two randomised trials",
  "uid": "c2fd7630-6a48-5956-9102-43dfd870dd2f"
}