Hypothesis: Oxidative Stress Score as a Combined Measure of Pro-oxidant and Antioxidant Exposures

Purpose To explore the hypothesis that a combination of several risk factors acting through the same pathway may produce an overall large increase in risk even in the presence of weak associations with each individual factor. Methods Using oxidative stress pathway as an example, we propose an oxidative stress score (OSS), where high and low pro-oxidant exposures expressed as continuous variables are assigned values of 0 and 1, while high and low antioxidant exposures are assigned values of 1 and 0, respectively. Dichotomous variables for pro-oxidant and antioxidant exposures are scored in a similar fashion. All individual scores are then summed to calculate the overall OSS, where higher and lower values indicate a shift toward antioxidant and pro-oxidant exposures, respectively. Results We illustrate this approach by using data from two previously-conducted case-control studies: a colonoscopy-based colorectal adenoma study, and a population-based prostate cancer study. In this pilot illustration we found a substantial decrease in risk associated with a high OSS for both prostate cancer and colorectal adenoma. By contrast, analyses for individual OSS components demonstrated no discernible pattern. Conclusions Our exploratory analyses serve as a demonstration of a method and warrant further confirmation on a larger scale.