Abstract
BACKGROUND: Recent studies suggest a possible link between Helicobacter pylori (H. pylori) infection and risk of colorectal cancer. We examined the association between H. pylori infection, anti-H. pylori treatment, and colorectal cancer and its precursor, adenoma, based on an observational study and a meta-analysis. METHODS: The observational study part included 3475 participants undergoing colonoscopy and H. pylori testing within the framework of a screening program in Zhejiang Province, China between March 8 and December 29, 2023. Logistic regression models were used to analyze the associations between H. pylori infection and the risk of colorectal cancer and adenoma. Additionally, a meta-analysis was conducted on the associations of H. pylori infection, anti-H. pylori treatment and risk of colorectal cancer and adenoma. Three databases (PubMed, Embase, and Cochrane Library) were searched for relevant studies from inception up to April 9, 2025. Two reviewers independently screened records for eligibility, extracted summary-level data and assessed study quality. Random-effects models were used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Study quality was evaluated using the Newcastle-Ottawa Scale for case-control and cohort studies, and adhering to the Agency for Healthcare Research and Quality's recommendations for cross-sectional studies. Heterogeneity was quantified using I (2) statistics and subgroup analyses were conducted to identify potential sources. We used funnel plots to assess publication bias, and Duval and Tweedie's "trim-and-fill" analysis to correct potential bias. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation system. The protocol for meta-analysis was registered in PROSPERO (CRD42024566640). FINDINGS: The observational study found a statistically significant association between H. pylori infection and the odds of colorectal cancer (n = 31, OR = 2.57, 95% CI: 1.26-5.39) and adenoma (n = 1245, OR = 1.37, 95% CI: 1.19-1.59), especially for advanced adenoma (n = 486, OR = 1.94, 95% CI: 1.59-2.38), compared with normal or non-adenomatous lesions (n = 2199). Meta-analysis of this and 54 other studies, with a total of 48,945,236 participants, found that H. pylori infection was positively associated with colorectal cancer (OR = 1.59, 95% CI: 1.39-1.82, I (2) = 89%) and adenoma (OR = 1.47, 95% CI: 1.36-1.59, I (2) = 88%), especially with advanced adenoma (OR = 1.77, 95% CI: 1.56-2.00, I (2) = 65%). The OR of overall colorectal neoplasia (colorectal cancer or adenoma) was 1.49 (95% CI: 1.39-1.60, I (2) = 91%). Based on meta-analysis of 3 retrospective studies, anti-H. pylori treatment was associated with a reduced overall risk of colorectal neoplasia (OR = 0.44, 95% CI: 0.20-0.97, I (2) = 93%). INTERPRETATION: H. pylori infection may represent a significant risk factor for the development of colorectal cancer. The effect of anti-H. pylori treatment on colorectal cancer incidence and mortality necessitates further investigation through large-scale, randomized controlled trials with prolonged follow-up durations. FUNDING: This work was supported by National Natural Science Foundation of China (No. 82404341, No. 82273704), Noncommunicable Chronic Diseases-National Science and Technology Major Project (No. 2023ZD0501400-2023ZD0501402), Beijing Hospitals Authority's Ascent Plan (DFL20241102), Peking University Medicine Fund for World's Leading Discipline or Discipline Cluster Development (No. BMU2022XKQ004), Science Foundation of Peking University Cancer Hospital (No. BJCH2024BJ02), Healthy Zhejiang One Million People Cohort (K-20230085), German Research Foundation (DFG, GE 2042/24-1).