Intra-Person Variation of Urinary Biomarkers of Oxidative Stress and Inflammation

Background: Oxidative stress and inflammation have been linked to many chronic diseases including cancer and cardiovascular diseases. Urinary levels of F2-isoprostanes (F2-IsoPs), 2,3-dinor-5,6-dihydro-15-F2t-IsoP (15-F2t-IsoP-M), a major metabolite of F2-IsoPs, prostaglandin E2 metabolite (PGE-M), and leukotriene E4 (LTE4) have been proposed as biomarkers for oxidative stress and inflammation. However, little information is available regarding the intra-person variation of these biomarkers, hindering their application in epidemiologic studies. Methods: We evaluated the intra-person variation of these four urinary biomarkers among 48 randomly chosen participants of a validation study of a population-based cohort, the Shanghai Men's Health Study. Four spot urine samples, collected during each season over a 1-year period, were measured for these biomarkers. Results: The intraclass correlation coefficients for F2-IsoPs, 15-F2t-IsoP-M, PGE-M, and LTE4 were 0.69, 0.76, 0.67, and 0.64, respectively. The Spearman correlation coefficients, derived by using bootstrap analysis of single spot measurements and the average of the other three seasonal measurements, were 0.47, 0.60, 0.61, and 0.57 for F2-IsoPs, 15-F2t-IsoP-M, PGE-M, and LTE4. Except for high correlations between F2-IsoPs and 15-F2t-IsoP-M (r = 0.65), the other biomarkers were moderately correlated (r = 0.21-0.44). Conclusions: Our study results suggest that these four urinary biomarkers have relatively low intra-person variation over a 1-year period. Impact: Spot measurements of F2-IsoPs, 15-F2t-IsoP-M, PGE-M, and LTE4 could be useful as biomarkers of oxidative stress and inflammation status for epidemiologic studies. Cancer Epidemiol Biomarkers Prev; 19(4); 947–52. ©2010 AACR.

[1]  R. DuBois,et al.  The role of COX-2 in intestinal inflammation and colorectal cancer , 2010, Oncogene.

[2]  N. Rothman,et al.  Urinary Prostaglandin E2 Metabolite and Gastric Cancer Risk in the Shanghai Women's Health Study , 2009, Cancer Epidemiology, Biomarkers & Prevention.

[3]  N. Rothman,et al.  Oxidative stress, obesity, and breast cancer risk: results from the Shanghai Women's Health Study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  Carmela Conte,et al.  Oxidative stress-related aging: A role for prostate cancer? , 2009, Biochimica et biophysica acta.

[5]  J. Morrow,et al.  Levels of Prostaglandin E Metabolite and Leukotriene E4 Are Increased in the Urine of Smokers: Evidence that Celecoxib Shunts Arachidonic Acid into the 5-Lipoxygenase Pathway , 2009, Cancer Prevention Research.

[6]  J. Morrow,et al.  A Phase II Study of Celecoxib in Combination with Paclitaxel, Carboplatin, and Radiotherapy for Patients with Inoperable Stage IIIA/B Non–Small Cell Lung Cancer , 2009, Clinical Cancer Research.

[7]  Daniel F. Gudbjartsson,et al.  A variant associated with nicotine dependence, lung cancer and peripheral arterial disease , 2008, Nature.

[8]  W. Henderson,et al.  Mechanisms of disease: Leukotrienes , 2007 .

[9]  J. Morrow,et al.  Quantification of F2-isoprostanes as a biomarker of oxidative stress , 2007, Nature Protocols.

[10]  N. Rothman,et al.  Prospective study of urinary prostaglandin E2 metabolite and colorectal cancer risk. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  D. D. Billheimer,et al.  Urine PGE-M: A metabolite of prostaglandin E2 as a potential biomarker of advanced colorectal neoplasia. , 2006, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[12]  D. Gozal,et al.  Urinary F2-isoprostane metabolite levels in children with sleep-disordered breathing , 2006, Sleep and Breathing.

[13]  S. Sheps,et al.  Specific comorbidity risk adjustment was a better predictor of 5-year acute myocardial infarction mortality than general methods. , 2006, Journal of clinical epidemiology.

[14]  J. Morrow,et al.  F2-Isoprostanes as markers of oxidative stress in vivo: An overview , 2005, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[15]  J. Morrow,et al.  Quantification of the major urinary metabolite of PGE2 by a liquid chromatographic/mass spectrometric assay: determination of cyclooxygenase-specific PGE2 synthesis in healthy humans and those with lung cancer. , 2004, Analytical biochemistry.

[16]  K. O'Reilly,et al.  Cigarette smoke induces cyclooxygenase-2 and microsomal prostaglandin E2 synthase in human lung fibroblasts: implications for lung inflammation and cancer. , 2004, American journal of physiology. Lung cellular and molecular physiology.

[17]  R. DuBois,et al.  Cyclooxygenase-2: a potential target in breast cancer. , 2004, Seminars in oncology.

[18]  B. Ainsworth,et al.  Reproducibility and validity of the Shanghai Women's Health Study physical activity questionnaire. , 2003, American journal of epidemiology.

[19]  J. Elias,et al.  Interleukin-13 and leukotrienes: an intersection of pathogenetic schema. , 2003, American journal of respiratory cell and molecular biology.

[20]  T. Montine,et al.  Improved assay for the quantification of the major urinary metabolite of the isoprostane 15-F(2t)-Isoprostane (8-iso-PGF(2alpha)) by a stable isotope dilution mass spectrometric assay. , 2001, Clinica chimica acta; international journal of clinical chemistry.

[21]  L. Packer,et al.  Handbook of Antioxidants , 2001 .

[22]  G. Wennergren Inflammatory mediators in blood and urine. , 2000, Paediatric respiratory reviews.

[23]  J. Morrow,et al.  Measurement of F(2)-isoprostanes as an index of oxidative stress in vivo. , 2000, Free radical biology & medicine.

[24]  J. Drazen,et al.  The biology of 5-lipoxygenase: function, structure, and regulatory mechanisms. , 1999, Proceedings of the Association of American Physicians.

[25]  G. FitzGerald,et al.  Alcohol-induced generation of lipid peroxidation products in humans. , 1999, The Journal of clinical investigation.

[26]  J. Manson,et al.  Reproducibility of plasma hormone levels in postmenopausal women over a 2-3-year period. , 1995, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[27]  J. Morrow,et al.  Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. Smoking as a cause of oxidative damage. , 1995, The New England journal of medicine.

[28]  B Rosner,et al.  Correction of logistic regression relative risk estimates and confidence intervals for random within-person measurement error. , 1992, American journal of epidemiology.

[29]  J. Morrow,et al.  A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Robert A. Lewis,et al.  Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. , 1990, The New England journal of medicine.

[31]  Barry Halliwell,et al.  Oxidative stress and cancer: have we moved forward? , 2007, The Biochemical journal.

[32]  C. Mackenzie,et al.  A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. , 1987, Journal of chronic diseases.