Oxidative Balance Scores and Risk of Incident Colorectal Cancer in a US Prospective Cohort Study

Although oxidative stress is implicated in colorectal carcinogenesis, human studies on associations of individual prooxidants and antioxidants with colorectal cancer (CRC) have been inconclusive. We incorporated individual environmental factors known to affect oxidative stress into 4 oxidative balance scores (OBS) and investigated their associations with CRC in the Cancer Prevention Study II Nutrition Cohort. During 1999–2009, a total of 1,109 incident CRC cases were identified among 80,063 participants in the Nutrition Cohort who had completed detailed questionnaires. Four OBS with different weighting methods (equal weights, literature review–based, a posteriori data-based, and weights based on Bayesian analysis) were created by combining 16 dietary and nondietary lifestyle factors. Higher values for all 4 OBS, representing more antioxidant exposures than prooxidant exposures, were associated with 41%–53% lower risks of CRC; for example, the relative risk for the highest OBS quartile versus the lowest in the Bayesian analysis was 0.50 (95% confidence interval: 0.41, 0.61). The associations were more modest when OBS was restricted to either dietary or nondietary components. These results, obtained using comprehensive summary measures of oxidative balance—especially considering the similarity of the findings derived using the different weighting methods—support the hypothesis that a predominance of antioxidant lifestyle exposures (both dietary and nondietary) over prooxidant lifestyle exposures reduces risk of CRC.