Helicobacter pylori infection, treatment and colorectal cancer risk by genetic predisposition: evidence from two randomised trials
Year: 2026
Type: article
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.
Source: Gut
Authors: Xuan Han, Heng-Min Xu, Zong-Chao Liu, Lian Zhang, Zhi-Qiang Hu, Wen-Jing Zhao, Ji-Er Zhao, Feng-Rui Zhu, Wei-dong Liu, Jun-Ling Ma, Yang Zhang, Jian-Xi Wang, Lei Zhang, Lan-Fu Zhang, Ming Li, Le-Hua Wang, Tong Zhou, Wei-Xiang Guan, Raquel Mejías-Luque, Wei-Cheng You, Markus Gerhard, Kai-Feng Pan, Wen-Qing Li
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Deutsches Zentrum für Infektionsforschung, National Natural Science Foundation of China, Bundesministerium für Bildung und Forschung, China Postdoctoral Science Foundation, Peking University, Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support, National Science and Technology Major Project, National Institutes of Health, National Key Research and Development Program of China, National Cancer Institute
Awards: G1163891290, G128804811, G1313450804, G2221658231, Etablierung eines Referenzlabors für Helicobacter-assoziierte Magenkarzinome, G3049523052, G3106377900, G3431494869, G4288399427, G4609004441, G5926259797, G6532049373, G6745825829, G7186545394, G7335125138, G7524867060, G7538024572, G7802401600, G8876768190
OpenAlex ID: W7166706467