Authors' Affiliations: International Epidemiology Institute, Rockville, Maryland; Division of Epidemiology, Department of Medicine; Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee; Section for Pharmacology, Institute of Medicine, University of Bergen; Laboratory of Clinical Biochemistry, Haukeland University Hospital; BEVITAL, Bergen, Norway; Department of Epidemiology, Harvard School of Public Health; and Dana-Farber/Harvard Cancer Center, Boston, Massachusetts.
Cancer Epidemiol Biomarkers Prev. 2013 Oct;22(10):1894-9. doi: 10.1158/1055-9965.EPI-13-0420. Epub 2013 Aug 15.
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 these markers and whether or not the use of a single measure 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 (κ) 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.
人们对碳代谢（OCM）与致癌作用之间的关系产生了浓厚的兴趣，这导致相关生物标志物的使用也越来越多，这些标志物被用来作为暴露的衡量指标。然而，人们对于这些标志物的个体内变异性知之甚少，也不知道使用单一的衡量指标是否适合评估流行病学研究中的暴露-疾病关系。我们评估了 147 名非裔美国人和 68 名非西班牙裔白人参与者的个体内血浆 19 种 OCM 生物标志物的浓度变化，这些参与者来自南方社区队列研究，他们在 2005 年至 2008 年期间两次献血并回答了调查问卷。我们计算了加权kappa 系数（κ）来评估基于重复测量的四分位数分配之间的一致性。还使用了调整后的组内相关系数（ICC）来评估两次测量的一致性。在这两个时间点，大多数（16/19）OCM 生物标志物的四分位数分配都显示出中等或更好的一致性，只有蛋氨酸、蛋氨酸亚砜和胱硫醚的 κ 值≤0.40。19 种生物标志物的中位数调整 ICC 为 0.60。黄素单核苷酸的重现性最高[ICC=0.84，95%置信区间（CI）0.79-0.87]，蛋氨酸及其氧化产物蛋氨酸亚砜的重现性最低[ICC=0.22，95%CI 0.09-0.34；ICC=0.20，95%CI 0.07-0.32]。总体而言，非裔美国人和白人、男性和女性的 OCM 生物标志物的个体内变异性相似。我们的研究结果表明，除了蛋氨酸和蛋氨酸亚砜之外，OCM 生物标志物通常具有良好的个体内重现性，可以被认为是流行病学研究中可靠的暴露测量指标。
