A Prospective Case-Control Study of Helicobacter pylori and Systemic Inflammation in Colorectal Cancer Pathogenesis

Background The role of Helicobacter pylori in colorectal cancer (CRC) remains controversial, while systemic inflammation drives carcinogenesis. We evaluated independent and interactive associations of active H. pylori infection and neutrophil-to-lymphocyte ratio (NLR) with CRC risk. Methods This prospective case-control study at Jinnah Hospital, Lahore, Pakistan, from August 2023 to August 2025, enrolled 105 treatment-naïve CRC patients and 210 age- and sex-matched controls with normal colonoscopy. Active H. pylori infection was determined by stool antigen testing. NLR was dichotomized at the cohort median (2.5). Multivariate logistic regression simultaneously adjusted for age, sex, smoking, diabetes, and body mass index. Results H. pylori prevalence did not differ between cases (58/105, 55.2%) and controls (105/210, 50.0%) (χ² = 0.769, p = 0.380). High NLR (>2.5) was present in 66/105 (62.9%) cases vs. 18/210 (8.6%) controls (χ² = 105.487, p < 0.001). After adjustment, high NLR was strongly associated with CRC (aOR = 300.86; 95% CI: 60.85-1487.58; p < 0.001; AUC = 0.792). The extremely wide confidence interval reflects sparse data (only 18 controls had high NLR), warranting cautious interpretation. A significant negative interaction was observed between H. pylori and high NLR (aOR = 0.245; 95% CI: 0.131-0.459; p < 0.001). The model explained 52.5% of variance (Nagelkerke R²) and correctly classified 83.5% of participants. Conclusion Elevated NLR is strongly associated with CRC in this Pakistani cohort, while active H. pylori infection shows no significant direct association. The negative interaction suggests host inflammatory status may modify H. pylori effects, though confirmation in larger studies is needed. Because of the case-control design with NLR measured after CRC diagnosis, reverse causation cannot be excluded. NLR measurement offers a simple, cost-effective tool for CRC risk stratification.