Helicobacter pylori, peptic ulcer disease, and colorectal cancer: a prospective study with genome-wide interaction analysis and Mendelian randomization
Menée au Royaume-Uni à l'aide d'une méthode de randomisation mendélienne portant sur des données concernant 492 490 personnes (durée médiane de suivi : 14,7 ans), cette étude analyse l'association entre une infection par Helicobacter pylori, un ulcère gastroduodénal et le risque de cancer colorectal
Introduction: Helicobacter pylori (HP) is a well-established gastric carcinogen. But it shows inconsistent association with colorectal cancer (CRC) across diverse study populations.
Methods: We investigated participants from the UK biobank. HP-seropositive cases and peptic ulcer diseases (PUDs) were identified. The primary outcome was CRC. We estimated the cumulative incidence using a competing risk model measured by the hazard ratios (HRs) with 95% confidence intervals (CIs) with adjustment. We did a genome-wide interaction analysis to identify genetic variants that modify HP-serology-CRC associations with exploratory gene-based and gene-set analysis. We further did a bidirectional two-sample Mendelian randomization (MR) to investigate the causal relation of gene-proxied PUD on CRC of the European ancestry and of the East Asian ancestry.
Results: We included 492,490 participants with a median follow-up of 14.7 years. HP sero-positivity did not significantly increase the incidence of CRC (adjusted HR = 0.76, 95% CI 0.53 − 1.10, p = 0.15). No SNP was identified to be significantly interacted with HP serology to modify CRC risk. The risk of CRC for PUD cases was not significantly different from non-PUD cases after adjusting (adjusted HR = 0.88, 95% CI 0.76 − 1.02, p = 0.09). The gene-proxied PUD causally increased the incidence of colon cancer of the East Asian ancestry (OR = 1.47, 95% CI = 1.00 − 2.15, p = 0.047), not of the European ancestry (OR = 1.03, 95% CI = 0.79 − 1.34, p = 0.82).
Conclusions: Neither seropositivity for HP nor PUD showed a robust increase on the risk of CRC in a 15-year follow-up. The causal relation of PUD on CRC was significant of East Asian ancestry, not of European ancestry.
Infectious Agents and Cancer , résumé, 2025