A Novel Application of Structural Equation Modeling Estimates the Association between Oxidative Stress and Colorectal Adenoma

In vitro evidence implicates oxidative stress in many adverse health conditions, including colorectal neoplasia. In human studies, however, oxidative stress is measured by imperfect biomarkers, which are inconsistently associated with health outcomes. Structural equation modeling (SEM) offers one possible solution by modeling a latent (unobserved) construct from multiple biomarkers. Our goal was to investigate the association of a latent oxidative stress variable with colorectal adenoma. Using SEM, we analyzed pooled data from two cross-sectional studies of colorectal adenoma (n=526) that measured five plasma biomarkers of oxidative stress and inflammation that comprised the latent oxidative stress variable: F2-isoprostanes (FIP), fluorescent oxidation products (FOP), mitochondrial DNA (MtDNA) copy number, -tocopherol (Gtoc), and C-reactive protein (CRP). Higher levels of oxidative stress were associated with colorectal adenoma (odds ratio=3.23 per standard deviation increase in oxidative stress, 95% confidence interval: 1.28, 8.18). The latent variable estimate was considerably stronger than the associations of adenoma with the individual biomarkers, which were modest and mostly non-significant. Risk factors were associated with adenoma via the oxidative stress pathway, particularly overweight and obesity with an OR=1.50, 95% CI: 1.10, 2.81; and OR=2.95, 95% CI: 1.28, 12.45, respectively. Oxidative stress may be positively associated with colorectal adenoma and important risk factors may act through this mechanism, but the cross-sectional design of the current study precludes observing the directionality of associations. The presence of an adenoma could affect levels of the circulating biomarkers thus we should be cautious of strong conclusions until the findings are replicated in a follow-up study.

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