# Inflammatory Cytokines and Oxidative Stress Markers in Relation to Colorectal Cancer Risk: A Case–Cohort Study in a Korean Population

## TL;DR

High levels of certain blood markers linked to inflammation and stress are tied to a higher risk of colorectal cancer in a Korean population.

## Contribution

Identifies specific inflammatory and oxidative stress markers associated with colorectal cancer risk in a Korean population.

## Key findings

- Higher blood levels of IL-6, IL-1β, and IFN-γ were strongly linked to increased colorectal cancer risk.
- Obesity modified the relationship between some markers and cancer risk, with TNF-α and IL-10 showing stronger associations in obese individuals.
- Reactive oxygen species showed no significant association with colorectal cancer risk.

## Abstract

Long-term inflammation and oxidative stress are thought to increase the risk of colorectal cancer (CRC), but evidence from Asian populations is still limited. In this study, we investigated whether blood levels of inflammation-related and oxidative stress-related markers are linked to the future development of CRC in a Korean population. We found that individuals with higher levels of certain inflammatory markers in their blood had a substantially higher risk of developing CRC during follow-up. Some markers were associated with cancer risk regardless of body weight, while others showed stronger associations only among people with obesity, suggesting that excess body fat may influence inflammation-related cancer risk. These results indicate that blood-based markers of inflammation and oxidative stress may help identify people at higher risk of CRC before diagnosis and improve our understanding of how chronic inflammation contributes to cancer development.

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.