Inflammatory Cytokines and Oxidative Stress Markers in Relation to Colorectal Cancer Risk: A Case-Cohort Study in a...

Background/Objectives: Chronic inflammation and oxidative stress are key contributors to colorectal cancer (CRC) development. However, prospective evidence in Asian populations remains limited. This study aimed to investigate the associations between circulating inflammatory cytokines, oxidative markers, and CRC risk in a Korean population. Methods: We conducted a case-cohort study nested within the Korean National Cancer Community (KNCCC) Cohort to investigate associations between inflammatory cytokines, oxidative stress markers, and CRC risk. A total of 128 incident CRC cases and 822 subcohort participants were included. Serum levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-1β, interferon-γ (IFN-γ), IL-10, reactive oxygen species (ROS), and nitric oxide (NO) were measured. Hazard ratios (HRs) were estimated using the Cox proportional hazards models with Barlow's weighting. Results: Higher serum IL-6 levels were strongly associated with increased CRC risk, with HRs of 6.20 (95% CI: 2.38-16.19), 8.31 (3.24-21.33), and 10.22 (3.95-26.46) for the second through fourth quartiles, compared to the lowest. Detectable levels of IL-1β and IFN-γ were also significantly associated with CRC risk (HRs: 2.16 and 1.53, respectively). Stratified analysis showed that IL-6 and IL-1β were associated with CRC risk in both obese and non-obese participants, while TNF-α, IL-10, and NO were associated with increased risk only among obese individuals. No significant associations were observed for ROS. Conclusions: Elevated levels of inflammatory cytokines (IL-6, IL-1β, IFN-γ) and NO were associated with higher CRC risk, suggesting their potential as early biomarkers. Obesity may modify the associations between certain markers and CRC risk. These findings highlight the role of systemic inflammation and oxidative stress in colorectal carcinogenesis.