Cope EL, Shrubsole MJ, Cohen SS, Cai Q, Wu J, Sonderman JS, Blot WJ, Signorello LB. 2013. Intra-individual variation in one-carbon metabolism biomarkers. Cancer Epidemiol Biomarkers Prev 22(10):1894–1899.
Interest in the relationship between one-carbon metabolism (OCM) and carcinogenesis is intensifying, leading to increased use of related biomarkers as measures of exposure. Little is known, however, about intra-individual variation in these markers and if use of a single measure is appropriate for assessing exposure-disease relationships in epidemiologic studies. We evaluated intra-individual variation in plasma concentrations of 19 OCM biomarkers in a sample of 147 African American and 68 non-Hispanic white participants from the Southern Community Cohort Study who donated blood samples and responded to questionnaires at two points in time from 2005–2008. Weighted kappa coefficients (κ) were calculated to assess agreement between quartile assignments based on the repeated measures. Adjusted intra-class correlation coefficients (ICCs) were also used to assess the consistency of the two measurements. Most (16 of 19) OCM biomarkers showed moderate or better agreement for quartile assignment at the two timepoints, with only methionine, methionine sulfoxide, and cystathionine having κ ≤ 0.40. The median adjusted ICC across the 19 biomarkers was 0.60. Reproducibility was highest for flavin mononucleotide (ICC=0.84, 95% confidence interval (CI) 0.79–0.87) and lowest for methionine and its oxidative product methionine sulfoxide (ICC=0.22, 95%CI 0.09–0.34; ICC=0.20, 95%CI 0.07–0.32, respectively). Overall, intra-individual variation in OCM biomarkers was similar for African Americans and whites, and for males and females. Our results suggest that, with the exception of methionine and methionine sulfoxide, OCM biomarkers generally have good intra-individual reproducibility and can be considered reliable exposure measures in epidemiologic studies.