Relationship between Urinary 15-F2t-Isoprostane and 8-Oxodeoxyguanosine Levels and Breast Cancer Risk

To evaluate the role of oxidative stress in breast cancer, we measured urinary levels of 15-F2t-isoprostane (15-F2t-IsoP) and 8-oxodeoxyguanosine (8-oxodG) in 400 cases and 401 controls, participants of the Long Island Breast Cancer Study Project. We also analyzed the effect of different factors that are associated with oxidative stress and might influence 15-F2t-IsoP and 8-oxodG levels. We observed a statistically significant trend in breast cancer risk with increasing quartiles of 15-F2t-IsoP levels [odds ratio (OR), 1.25; 95% confidence interval (95% CI), 0.81-1.94; OR, 1.53; 95% CI, 0.99-2.35; OR, 1.88; 95% CI, 1.23-2.88, for the 2nd, 3rd, and 4th quartile relative to the lowest quartile, respectively; Ptrend = 0.002]. Although it is possible that increased levels may reflect the stress associated with recent treatment, the positive association was also observed when the analyses were restricted to case women for whom chemotherapy and radiation therapy had not yet been initiated at the time of the urine collection. The association with the highest quartile compared with lowest quartile of 15-F2t-IsoP was similar across strata of age, physical activity, fruit and vegetable intake, alcohol intake, cigarette smoking, body mass index, and menopausal status. We did not observe any association of breast cancer risk with 8-oxodG levels, but when cases with radiation treatment were removed from the analysis, a significant inverse trend (P = 0.04) was observed. Among controls, levels of 15-F2t-IsoP were higher among current cigarette smokers but did not differ by the amount of physical activity, fruit and vegetable intake, alcohol intake, body mass index, and menopausal status. Among controls, levels of 8-oxodG were higher among postmenopausal women and current and former cigarette smokers but did not differ by the other factors. In summary, our results suggest that urinary markers of lipid peroxidation and oxidative DNA damage may be associated with breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(4):639-44)

[1]  Mary Beth Terry,et al.  Lifetime alcohol intake and breast cancer risk. , 2006, Annals of epidemiology.

[2]  A. Neugut,et al.  Body size changes in relation to postmenopausal breast cancer among women on Long Island, New York. , 2005, American journal of epidemiology.

[3]  M. Evans,et al.  DNA repair is responsible for the presence of oxidatively damaged DNA lesions in urine. , 2005, Mutation research.

[4]  C. Rock,et al.  Diet and Biomarkers of Oxidative Damage in Women Previously Treated for Breast Cancer , 2005, Nutrition and cancer.

[5]  I. Näslund,et al.  Extracellular 8-oxo-dG as a sensitive parameter for oxidative stress in vivo and in vitro , 2005, Free radical research.

[6]  A. Neugut,et al.  Environmental tobacco smoke and breast cancer incidence. , 2004, Environmental research.

[7]  A. Neugut,et al.  Fruits, vegetables, and micronutrients in relation to breast cancer modified by menopause and hormone receptor status. , 2004, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[8]  D. Johnston,et al.  High levels of oxidative DNA damage in lymphocyte DNA of premenopausal breast cancer patients from Egypt , 2004, International journal of environmental health research.

[9]  H. Miyake,et al.  Oxidative DNA damage in patients with prostate cancer and its response to treatment. , 2004, The Journal of urology.

[10]  P. Leanderson,et al.  Urinary excretion of 8-hydroxydeoxyguanosine and malondialdehyde after high dose radiochemotherapy preceding stem cell transplantation. , 2004, Free radical biology & medicine.

[11]  J. Klaunig,et al.  The role of oxidative stress in carcinogenesis. , 2004, Annual review of pharmacology and toxicology.

[12]  C. Heward,et al.  Urinary excretion of three nucleic acid oxidation adducts and isoprostane F(2)alpha measured by liquid chromatography-mass spectrometry in smokers, ex-smokers, and nonsmokers. , 2003, Free radical biology & medicine.

[13]  S. Kamohara,et al.  Oxidative DNA damage (8-hydroxydeoxyguanosine) and body iron status: a study on 2507 healthy people. , 2003, Free radical biology & medicine.

[14]  Edward Krieg,et al.  Effect of perchloroethylene, smoking, and race on oxidative DNA damage in female dry cleaners. , 2003, Mutation research.

[15]  K. Tsao,et al.  Urinary 8-hydroxydeoxyguanosine and its analogs as DNA marker of oxidative stress: development of an ELISA and measurement in both bladder and prostate cancers. , 2003, Clinica chimica acta; international journal of clinical chemistry.

[16]  F. Sung,et al.  Oxidative DNA damage estimated by urinary 8-hydroxydeoxyguanosine: influence of taxi driving, smoking and areca chewing. , 2003, Chemosphere.

[17]  Y. Hsueh,et al.  Association of hepatitis virus infection, alcohol consumption and plasma vitamin A levels with urinary 8-hydroxydeoxyguanosine in chemical workers. , 2003, Mutation research.

[18]  E. Benjamin,et al.  Obesity and Systemic Oxidative Stress: Clinical Correlates of Oxidative Stress in The Framingham Study , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[19]  W. D. Jackson,et al.  Antioxidant status of young children: response to an antioxidant supplement. , 2002, Journal of the American Dietetic Association.

[20]  J. Cracowski,et al.  Isoprostanes as a biomarker of lipid peroxidation in humans: physiology, pharmacology and clinical implications. , 2002, Trends in pharmacological sciences.

[21]  Mary Beth Terry,et al.  The Long Island Breast Cancer Study Project: Description of a Multi-Institutional Collaboration to Identify Environmental Risk Factors for Breast Cancer , 2002, Breast Cancer Research and Treatment.

[22]  Y. Ogawa,et al.  Moderate alcohol consumption reduces urinary 8-hydroxydeoxyguanosine by inducing of uric acid. , 2001, Industrial health.

[23]  A. Sahin,et al.  Oxidative DNA damage and 8‐hydroxy‐2‐deoxyguanosine DNA glycosylase/apurinic lyase in human breast cancer , 2001, Molecular carcinogenesis.

[24]  A. Bast,et al.  A vegetable/fruit concentrate with high antioxidant capacity has no effect on biomarkers of antioxidant status in male smokers. , 2001, The Journal of nutrition.

[25]  B. Palumbo,et al.  Increase of isoprostane 8-epi-PGF2 αafter restarting smoking , 2001 .

[26]  Y. Ozkan,et al.  Plasma malondialdehyde (MDA) levels in breast and lung cancer patients , 2001, Journal of clinical pharmacy and therapeutics.

[27]  Alexander Pilger,et al.  Longitudinal study of urinary 8-hydroxy-2′-deoxyguanosine excretion in healthy adults , 2001, Free radical research.

[28]  T. Nagakura,et al.  Smoking and oxidant stress: assay of isoprostane in human urine by gas chromatography-mass spectrometry. , 2000, Journal of chromatography. B, Biomedical sciences and applications.

[29]  B. Palumbo,et al.  Quitting cigarette smoking results in a fast improvement of in vivo oxidation injury (determined via plasma, serum and urinary isoprostane). , 2000, Thrombosis research.

[30]  H. Thompson,et al.  Effect of increased vegetable and fruit consumption on markers of oxidative cellular damage. , 1999, Carcinogenesis.

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

[32]  M. Niculescu,et al.  Plasma levels of 8-epiPGF2alpha, an in vivo marker of oxidative stress, are not affected by aging or Alzheimer's disease. , 1999, Free radical biology & medicine.

[33]  L. Beilin,et al.  Measurement of Urinary F2-Isoprostanes as Markers of in Vivo Lipid Peroxidation—A Comparison of Enzyme Immunoassay with Gas Chromatography/Mass Spectrometry , 1999 .

[34]  G. FitzGerald,et al.  IPF2α-I: An index of lipid peroxidation in humans , 1998 .

[35]  P. Kellokumpu-Lehtinen,et al.  Biomarker evidence of DNA oxidation in lung cancer patients: association of urinary 8‐hydroxy‐2′‐deoxyguanosine excretion with radiotherapy, chemotherapy, and response to treatment , 1997, FEBS letters.

[36]  K. Dhingra,et al.  Lipid peroxidation-induced putative malondialdehyde-DNA adducts in human breast tissues. , 1996, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[37]  M. Reilly,et al.  Modulation of oxidant stress in vivo in chronic cigarette smokers. , 1996, Circulation.

[38]  G. FitzGerald,et al.  Immunological characterization of urinary 8-epi-prostaglandin F2 alpha excretion in man. , 1995, The Journal of pharmacology and experimental therapeutics.

[39]  F. Perera,et al.  Determination of 8-hydroxydeoxyguanosine by an immunoaffinity chromatography-monoclonal antibody-based ELISA. , 1995, Free radical biology & medicine.

[40]  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.

[41]  J. Morrow,et al.  Non-cyclooxygenase-derived prostanoids (F2-isoprostanes) are formed in situ on phospholipids. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[42]  D. Hosmer,et al.  Applied Logistic Regression , 1991 .

[43]  Joseph F. Williams.  Annual Review of Pharmacology , 1975 .

[44]  J. Fleiss,et al.  Statistical methods for rates and proportions , 1973 .

[45]  S. Batra,et al.  Lipid peroxidation, free radical production and antioxidant status in breast cancer , 2004, Breast Cancer Research and Treatment.

[46]  P. Chang,et al.  Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. , 2004, Clinica chimica acta; international journal of clinical chemistry.

[47]  Cancer Epidemiol Biomarkers Prev , 2004 .

[48]  S. Basu,et al.  Prostaglandin F2α metabolite and F2-isoprostane excretion rates in migraine , 2002 .

[49]  P. Dolara,et al.  Levels of 8-hydroxydeoxyguanosine as a marker of DNA damage in human leukocytes. , 2000, Free radical biology & medicine.

[50]  C. Ambrosone.  Oxidants and antioxidants in breast cancer. , 2000, Antioxidants & redox signaling.

[51]  L. Beilin,et al.  Measurement of urinary F(2)-isoprostanes as markers of in vivo lipid peroxidation-A comparison of enzyme immunoassay with gas chromatography/mass spectrometry. , 1999, Analytical biochemistry.

[52]  A. Favier,et al.  Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine and 5-(hydroxymethyl) uracil in smokers. , 1999, Free radical research.

[53]  M. Baraldi,et al.  Measurement of urinary 8-Epi-prostaglandin F2alpha, a novel index of lipid peroxidation in vivo, by immunoaffinity extraction/gas chromatography-mass spectrometry. Basal levels in smokers and nonsmokers. , 1996, Free radical biology & medicine.