Time-dependent relationship between urinary biomarkers of nucleic acid oxidation and colorectal cancer risk

作者：Yingya Zhao, Marina Sayuri Nogueira, Ginger L. Milne, Yu-Tang Gao, Qiuyin Cai, Qing Lan, Haoyang Yi, Nathaniel Rothman, Xiao-Ou Shu, Wei Zheng, Qingxia Chen, Gong Yang · 发表于：JNCI Journal of the National Cancer Institute · 年份：2025 · DOI：10.1093/jnci/djaf312 · 被引用次数：1 · 研究领域：Antioxidant Activity and Oxidative Stress、DNA Repair Mechanisms、Carcinogens and Genotoxicity Assessment

BACKGROUND: Experimental models indicate that oxidative stress may shift from promoting to suppressing tumor development as cancer progresses. METHODS: We conducted a nested case-control study within 2 Shanghai cohorts for primary analysis and 1 US cohort for replication. Over a median follow-up of 15.1 years in the Shanghai cohorts, 1938 incident colorectal cancer (CRC) cases were identified and matched to 1 control each. In the US cohort, 251 incident CRC cases were matched to 2 controls each. Systemic oxidative stress was assessed using urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2'-deoxyguanosine [8-oxo-dG]) and RNA oxidation (7,8-dihydro-8-oxo-guanosine [8-oxo-Guo]) via ultra-performance liquid chromatography tandem mass spectrometry. Multivariable-adjusted odds ratios for CRC risk were calculated. RESULTS: After adjusting for selected covariates, an inversion association between oxidative stress markers and CRC risk was observed in the Shanghai cohorts and independently replicated in the US cohort. This inverse association was time-dependent, manifesting only for CRC cases diagnosed within 5 years following enrollment. Odds ratios for CRC at the 10th and 90th percentiles of 8-oxo-dG levels, relative to the median, were 1.87 (95% confidence interval [CI] = 1.39 to 2.53) and 0.48 (95% CI = 0.37 to 0.63), respectively, demonstrating a threefold difference in risk, with a P value for overall association less than .001. A similar pattern was observed for 8-oxo-Guo. N...