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Published on: July 28, 2010
Systemic Lipid Peroxidation and Colorectal Cancer Risk: A Time-Varying Relationship
Gong Yang1, Ginger L Milne2, Marina S Nogueira1,2
1Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
International Journal of Cancer
|June 16, 2026
Summary
High levels of systemic oxidative stress (OxS) are linked to lower colorectal cancer (CRC) risk, particularly in the short term. This suggests antioxidant supplements may pose risks for some individuals.
Area of Science:
- Biochemistry
- Oncology
- Epidemiology
Background:
- Randomized controlled trials have not confirmed antioxidant supplements' chemopreventive benefits for colorectal cancer (CRC).
- Prior research indicated a time-dependent inverse association between systemic oxidative stress (OxS) and CRC risk.
- This study investigated lipid peroxidation markers and a composite OxS index for improved CRC risk characterization.
Purpose of the Study:
- To assess the association between systemic lipid peroxidation and CRC risk.
- To evaluate if a composite OxS index improves CRC risk prediction.
- To examine the time-dependent relationship between OxS and CRC risk.
Main Methods:
- Nested case-control study in Shanghai and US cohorts.
- Assessed systemic lipid peroxidation using urinary F2-isoprostanes (F2-IsoPs) via UPLC-MS/MS.
- Employed conditional logistic regression to estimate odds ratios (ORs) for CRC risk.
Main Results:
- Lower levels of 5-F2t-IsoP were associated with increased CRC risk in both cohorts.
- A 2.2-fold difference in CRC risk was observed based on 5-F2t-IsoP levels within 5 years of enrollment.
- A composite OxS index revealed a 3.9-fold difference in CRC risk, with no significant associations for diagnoses beyond 5 years.
Conclusions:
- Systemic OxS is inversely and time-dependently associated with CRC risk, particularly in later disease development stages.
- High-dose antioxidant supplementation aimed at lowering OxS may carry unintended risks for high-risk individuals.
- Findings challenge the efficacy of antioxidant supplementation and highlight potential risks in CRC prevention.
