Bergen, Norway
Bergen, Norway

Time filter

Source Type

Cope E.L.,International Epidemiology Institute | Shrubsole M.J.,Vanderbilt University | Cohen S.S.,International Epidemiology Institute | Cai Q.,Vanderbilt University | And 7 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2013

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 the intraindividual variation in thesemarkers andwhether or not the use of a singlemeasure is appropriate for assessing exposure-disease relationships in epidemiologic studies. We evaluated the intraindividual 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 time points from 2005 to 2008. Weighted kappa coefficients (k) were calculated to assess the agreement between quartile assignments based on the repeated measures. Adjusted intraclass correlation coefficients (ICC) were also used to assess the consistency of the two measurements. Most (16/19) OCM biomarkers showed a moderate or better agreement for quartile assignment at the two time points, 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, the intraindividual 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 intraindividual reproducibility and can be considered as reliable exposure measures in epidemiologic studies. © 2013 American Association for Cancer Research.


Knowledge of stability during sample transportation and changes in biomarker concentrations within person over time are paramount for proper design and interpretation of epidemiologic studies based on a single measurement of biomarker status. Therefore, we investigated stability and intraindividual vs. interindividual variation in blood concentrations of biomarkers related to vitamin status, one-carbon metabolism, and the kynurenine pathway. Whole blood (EDTA and heparin, n = 12) was stored with an icepack for 24 or 48 h, and plasma concentrations of 38 biomarkers were determined. Stability was calculated as change per hour, intraclass correlation coefficient (ICC), and simple Spearman correlation. Within-person reproducibility of biomarkers was expressed as ICC in samples collected 1-2 y apart from 40 postmenopausal women and in samples collected up to 3 y apart from 551 patients with stable angina pectoris. Biomarker stability was similar in EDTA and heparin blood. Most biomarkers were essentially stable, except for choline and total homocysteine (tHcy), which increased markedly. Within-person reproducibility in postmenopausal women was excellent (ICC > 0.75) for cotinine, all-trans retinol, cobalamin, riboflavin, -tocopherol, Gly, pyridoxal, methylmalonic acid, creatinine, pyridoxal 5-phosphate, and Ser; was good to fair (ICC of 0.74-0.40) for pyridoxic acid, kynurenine, tHcy, cholecalciferol, flavin mononucleotide, kynurenic acid, xanthurenic acid, 3-hydroxykynurenine, sarcosine, anthranilic acid, cystathionine, homoarginine, 3-hydroxyanthranilic acid, betaine, Arg, folate, total cysteine, dimethylglycine, asymmetric dimethylarginine, neopterin, symmetric dimethylarginine, and Trp; and poor (ICC of 0.39-0.15) for methionine sulfoxide, Met, choline, and trimethyllysine. Similar reproducibilities were observed in patients with coronary heart disease. Thus, most biomarkers investigated were essentially stable in cooled whole blood for up to 48 h and had a sufficient within-person reproducibility to allow one-exposure assessment of biomarker status in epidemiologic studies. The Western Norway B Vitamin Intervention Trial was registered at clinicaltrials.gov as NTC00354081.

Loading BEVITAL collaborators
Loading BEVITAL collaborators