title: Using multiple biomarkers and determinants to obtain a better measurement of oxidative stress: a latent variable structural equation model approach.
abstract: OBJECTIVE
  Since oxidative stress involves a variety of cellular changes, no single biomarker can serve as a complete measure of this complex biological process. The analytic technique of structural equation modeling (SEM) provides a possible solution to this problem by modelling a latent (unobserved) variable constructed from the covariance of multiple biomarkers.
  
  
  METHODS
  Using three pooled datasets, we modelled a latent oxidative stress variable from five biomarkers related to oxidative stress: F2-isoprostanes (FIP), fluorescent oxidation products, mitochondrial DNA copy number, γ-tocopherol (Gtoc) and C-reactive protein (CRP, an inflammation marker closely linked to oxidative stress). We validated the latent variable by assessing its relation to pro- and anti-oxidant exposures.
  
  
  RESULTS
  FIP, Gtoc and CRP characterized the latent oxidative stress variable. Obesity, smoking, aspirin use and β-carotene were statistically significantly associated with oxidative stress in the theorized directions; the same exposures were weakly and inconsistently associated with the individual biomarkers.
  
  
  CONCLUSIONS
  Our results suggest that using SEM with latent variables decreases the biomarker-specific variability, and may produce a better measure of oxidative stress than do single variables. This methodology can be applied to similar areas of research in which a single biomarker is not sufficient to fully describe a complex biological phenomenon.
authors.affiliation: a Department of Epidemiology, Rollins School of Public Health , Emory University , Atlanta , GA , USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Eldridge
authors.affiliation: a Department of Epidemiology, Rollins School of Public Health , Emory University , Atlanta , GA , USA.|b Department of Biostatistics and Bioinformatics, Rollins School of Public Health , Emory University , Atlanta , GA , USA.
authors.forename: W Dana
authors.initials: WD
authors.lastname: Flanders
authors.affiliation: a Department of Epidemiology, Rollins School of Public Health , Emory University , Atlanta , GA , USA.|c Winship Cancer Institute, Emory University , Atlanta , GA , USA.
authors.forename: Roberd M
authors.initials: RM
authors.lastname: Bostick
authors.affiliation: a Department of Epidemiology, Rollins School of Public Health , Emory University , Atlanta , GA , USA.|c Winship Cancer Institute, Emory University , Atlanta , GA , USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Fedirko
authors.affiliation: d Department of Laboratory Medicine and Pathology, Epidemiology & Community Health , University of Minnesota , Minneapolis , MN , USA.
authors.forename: Myron
authors.initials: M
authors.lastname: Gross
authors.affiliation: d Department of Laboratory Medicine and Pathology, Epidemiology & Community Health , University of Minnesota , Minneapolis , MN , USA.
authors.forename: Bharat
authors.initials: B
authors.lastname: Thyagarajan
authors.affiliation: a Department of Epidemiology, Rollins School of Public Health , Emory University , Atlanta , GA , USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Goodman
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D002097:C-Reactive Protein / Q000032:analysis; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial; D028441:F2-Isoprostanes / Q000032:analysis; D006801:Humans; D008722:Methods; D008962:Models, Theoretical; D018384:Oxidative Stress; D024505:Tocopherols / Q000032:analysis
chemical_list: D015415:Biomarkers; D004272:DNA, Mitochondrial; D028441:F2-Isoprostanes; D002097:C-Reactive Protein; D024505:Tocopherols
keywords: Oxidative stress; anti-oxidant; biomarkers; latent variable; structural equation modeling