Helicobacter pylori infection, systemic inflammation, and colorectal cancer: A prospectively enrolled case–control study.

e15668 Background: The association between Helicobacter pylori (H. pylori) infection and colorectal cancer (CRC) remains controversial, with prior studies reporting heterogeneous findings. Systemic inflammation has been implicated in colorectal carcinogenesis and may influence this relationship. We evaluated the independent and combined associations of active H. pylori infection and systemic inflammation with CRC. Methods: From August 2023 to August 2025, we prospectively enrolled 105 treatment-naïve patients with histologically confirmed CRC and 210 age- and sex-matched colonoscopy-negative controls. Active H. pylori infection was assessed using stool antigen testing. Systemic inflammation was evaluated using the pre-treatment neutrophil-to-lymphocyte ratio (NLR), calculated from complete blood counts and dichotomized at the cohort median (2.5). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) for CRC after controlling for age, sex, smoking status, diabetes, and body mass index. An interaction term was included to assess effect modification between H. pylori infection and NLR. Results: The median age of participants was 62 years. H. pylori infection was detected in 38.1% (40/105) of CRC cases and 35.7% (75/210) of controls (p = 0.67). Elevated NLR ( > 2.5) was observed more frequently among CRC cases than controls (62.9% vs 28.6%, p < 0.001). In adjusted analyses, H. pylori infection was not associated with CRC (aOR 1.08; 95% CI, 0.65–1.80; p = 0.76). Elevated NLR was strongly associated with CRC (aOR 3.95; 95% CI, 2.38–6.56; p < 0.001). No statistically significant interaction was observed between H. pylori infection and elevated NLR (p for interaction = 0.42). Conclusions: In this prospectively enrolled case–control study, systemic inflammation, as reflected by elevated NLR, was strongly associated with colorectal cancer, whereas active H. pylori infection was not. These findings suggest that inflammatory status may be more relevant to CRC association than H. pylori infection alone and support further investigation of inflammatory biomarkers in colorectal cancer risk stratification.