Associations between Dietary Intake of Fruits and Vegetables in Relation to Urinary Estrogen DNA Adduct Ratio


Background: Estrogen exposure plays a role in breast cancer (BC) development. A novel estrogen biomarker, the estrogen DNA adduct (EDA) ratio, was shown to be elevated in women at high-risk of BC and among BC cases. Modifiable factors may impact the EDA ratio, with studies demonstrating that resveratrol reduces EDA ratio in vitro. We sought to examine the hypothesis that dietary intake of fruits and vegetables is inversely associated with EDA ratio. Methods: This analysis was conducted in 53 pre-menopausal, healthy women aged 40 - 45 years from a cross-sectional study in which participants provided first-void urine samples and 3-day food records. Urine samples were analyzed using ultra performance liquid chromatography/tandem mass spectrometry. The EDA ratio was calculated as the estrogen-DNA adducts divided by estrogen metabolites and conjugates. A trend test was used to assess associations between tertiles of dietary intake using linear regression. Results: After adjustment for age, total energy, percent adiposity, serum estradiol and estrone-sulfate, we observed inverse associations of EDA ratio with carbohydrate consumption (P = 0.01) and vegetable intake (P = 0.01). EDA ratio was inversely associated with 5 botanical groups (Chenopodiaceae: P = 0.02; Umbelliferae: P = 0.03; Compositae: P = 0.01; Ericaceae: P = 0.01; Musaceae: P = 0.03) but not fruit intake overall. Conclusion: Although these data require replication before conclusions are drawn, this report suggests an inverse association between vegetable and carbohydrate consumption and EDA ratio. Impact: While more information is still needed, these findings suggest a link between dietary intake and a biomarker that is both associated with high-risk BC status and associated with modifiable factors.

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Reding, K. , Zahid, M. , Cavalieri, E. , Rogan, E. , Raccor, B. , Atkinson, C. , Yong, M. , Newton, K. and Lampe, J. (2014) Associations between Dietary Intake of Fruits and Vegetables in Relation to Urinary Estrogen DNA Adduct Ratio. Open Journal of Preventive Medicine, 4, 429-437. doi: 10.4236/ojpm.2014.46050.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Feigelson, H. (2003) Breast Cancer: Epidemiology and Molecular Endocrinology. Hormones, Genes, and Cancer, Oxford University Press, New York, 120-138.
[2] Cavalieri, E., Frenkel, K., Liehr, J.G., Rogan, E. and Roy, D. (2000) Estrogens as Endogenous Genotoxic Agents— DNA Adducts and Mutations. Journal of the National Cancer Institute Monographs, 27, 75-93.
[3] Cavalieri, E.L. and Rogan, E.G. (2010) Depurinating Estrogen-DNA Adducts in the Etiology and Prevention of Breast and Other Human Cancers. Future Oncology, 6, 75-91.
[4] Cavalieri, E., Chakravarti, D., Guttenplan, J., et al. (2006) Catechol Estrogen Quinones as Initiators of Breast and Other Human Cancers: Implications for Biomarkers of Susceptibility and Cancer Prevention. Biochim Biophys Acta, 1766, 63-78.
[5] Cavalieri, E., Saeed, M., Zahid, M., et al. (2012) Mechanism of DNA Depurination by Carcinogens in Relation to Cancer Initiation. IUBMB Life, 64, 169-179.
[6] Cavalieri, E.L., Stack, D.E., Devanesan, P.D., et al. (1997) Molecular Origin of Cancer: Catechol Estrogen-3,4-Quinones as Endogenous Tumor Initiators. Proceedings of the National Academy of Sciences of the USA, 94, 10937-10942.
[7] Gaikwad, N., Yang, L., Muti, P., et al. (2009) Urine Biomarkers of Risk in the Molecular Etiology of Breast Cancer. Breast Cancer Basic Clinical Research, 3, 1-8.
[8] Gaikwad, N.W., Yang, L., Muti, P., et al. (2008) The Molecular Etiology of Breast Cancer: Evidence from Biomarkers of Risk. International Journal of Cancer, 122, 1949-1957.
[9] Pruthi, S., Yang, L., Sandhu, N.P., et al. (2012) Evaluation of Serum Estrogen-DNA Adducts as Potential Biomarkers for Breast Cancer Risk. The Journal of Steroid Biochemistry and Molecular Biology, 132, 73-79.
[10] Yager, JD. (2000) Endogenous Estrogens as Carcinogens through Metabolic Activation. Journal of the National Cancer Institute Monographs, 27, 67-73.
[11] Moon, Y.J., Wang, X. and Morris, M.E. (2006) Dietary Flavonoids: Effects on Xenobiotic and Carcinogen Metabolism. Toxicology in Vitro, 20, 187-210.
[12] Seow, A., Vainio, H. and Yu, M.C. (2005) Effect of Glutathione-S-Transferase Polymorphisms on the Cancer Preventive Potential of Isothiocyanates: An Epidemiological Perspective. Mutation Research, 592, 58-67.
[13] Jeffery, E.H. and Stewart, K.E. (2004) Upregulation of Quinone Reductase by Glucosinolate Hydrolysis Products from Dietary Broccoli. Methods in Enzymology, 382, 457-469.
[14] Lu, F., Zahid, M., Wang, C., Saeed, M., Cavalieri, E.L. and Rogan, E.G. (2008) Resveratrol Prevents Estrogen-DNA Adduct Formation and Neoplastic Transformation in MCF-10F Cells. Cancer Prevention Research (Phila), 1, 135-145.
[15] Yang, L., Zahid, M., Liao, Y., et al. (2013) Reduced Formation of Depurinating Estrogen-DNA Adducts by Sulforaphane or KEAP1 Disruption in Human Mammary Epithelial MCF-10A Cells. Carcinogenesis, 34, 2587-2592.
[16] Zahid, M., Saeed, M., Beseler, C., Rogan, E.G. and Cavalieri, E.L. (2011) Resveratrol and N-Acetylcysteine Block the Cancer-Initiating Step in MCF-10F Cells. Free Radical Biology & Medicine, 50, 78-85.
[17] Venugopal, D., Zahid, M., Mailander, P.C., et al. (2008) Reduction of Estrogen-Induced Transformation of Mouse Mammary Epithelial Cells by N-Acetylcysteine. The Journal of Steroid Biochemistry and Molecular Biology, 109, 22-30.
[18] Atkinson, C., Newton, K.M., Bowles, E.J., Yong, M. and Lampe, J.W. (2008) Demographic, Anthropometric, and Lifestyle Factors and Dietary Intakes in Relation to Daidzein-Metabolizing Phenotypes among Premenopausal Women in the United States. The American Journal of Clinical Nutrition, 87, 679-687.
[19] Horner, N.K., Kristal, A.R., Prunty, J., Skor, H.E., Potter, J.D. and Lampe, J.W. (2002) Dietary Determinants of Plasma Enterolactone. Cancer Epidemiology, Biomarkers & Prevention, 11, 121-126.
[20] Aiyer, H.S. and Gupta, R.C. (2010) Berries and Ellagic Acid Prevent Estrogen-Induced Mammary Tumorigenesis by Modulating Enzymes of Estrogen Metabolism. Cancer Prevention Research (Phila), 3, 727-737.
[21] Wang, L.S. and Stoner, G.D. (2008) Anthocyanins and Their Role in Cancer Prevention. Cancer Letters, 269, 281-290.
[22] Wu, X., Beecher, G.R., Holden, J.M., Haytowitz, D.B., Gebhardt, S.E. and Prior, R.L. (2006) Concentrations of Anthocyanins in Common Foods in the United States and Estimation of Normal Consumption. Journal of Agricultural and Food Chemistry, 54, 4069-4075.
[23] Saracino, M.R. and Lampe, J.W. (2007) Phytochemical Regulation of UDP-Glucuronosyltransferases: Implications for Cancer Prevention. Nutrition and Cancer, 59, 121-141.
[24] Bradlow, H.L., Michnovicz, J.J., Halper, M., Miller, D.G., Wong, G.Y. and Osborne, M.P. (1994) Long-Term Responses of Women to Indole-3-Carbinol or a High Fiber Diet. Cancer Epidemiology, Biomarkers & Prevention, 3, 591-595.
[25] Lu, L.J., Cree, M., Josyula, S., Nagamani, M., Grady, J.J. and Anderson, K.E. (2000) Increased Urinary Excretion of 2-Hydroxyestrone But Not 16 Alpha-Hydroxyestrone in Premenopausal Women during a Soya Diet Containing Isoflavones. Cancer Research, 60, 1299-1305.
[26] Haggans, C.J., Hutchins, A.M., Olson, B.A., Thomas, W., Martini, M.C. and Slavin, J.L. (1999) Effect of Flaxseed Consumption on Urinary Estrogen Metabolites in Postmenopausal Women. Nutrition and Cancer, 33, 188-195.
[27] Greenlee, H., Atkinson, C., Stanczyk, F.Z. and Lampe, J.W. (2007) A Pilot and Feasibility Study on the Effects of Naturopathic Botanical and Dietary Interventions on Sex Steroid Hormone Metabolism in Premenopausal Women. Cancer Epidemiology, Biomarkers & Prevention, 16, 1601-1609.
[28] Zahid, M., Gaikwad, N.W., Rogan, E.G. and Cavalieri, E.L. (2007) Inhibition of Depurinating Estrogen-DNA Adduct Formation by Natural Compounds. Chemical Research in Toxicology, 20, 1947-1953.
[29] Samuni, A.M., Chuang, E.Y., Krishna, M.C., et al. (2003) Semiquinone Radical Intermediate in Catecholic Estrogen-Mediated Cytotoxicity and Mutagenesis: Chemoprevention Strategies with Antioxidants. Proceedings of the National Academy of Sciences of the USA, 100, 5390-5395.
[30] Bonanomi, L. and Gazzaniga, A. (1980) Toxicological, Pharmacokinetic and Metabolic Studies on Acetylcysteine. European Journal of Respiratory Diseases, Supplement, 111, 45-51.
[31] Athar, M., Back, J.H., Tang, X., et al. (2007) Resveratrol: A Review of Preclinical Studies for Human Cancer Prevention. Toxicology and Applied Pharmacology, 224, 274-283.
[32] Turesky, R.J. (2004) The Role of Genetic Polymorphisms in Metabolism of Carcinogenic Heterocyclic Aromatic Amines. Current Drug Metabolism, 5, 169-180.
[33] Sugimura, T., Kawachi, T., Nagao, M., et al. (1977) Mutagenic Principle(s) in Tryptophan and Phenylalanine Pyrolysis Products. Proceedings of the Japan Academy, 53, 58-61.
[34] Yang, Y.J., Kim, M.K., Hwang, S.H., Ahn, Y., Shim, J.E. and Kim, D.H. (2010) Relative Validities of 3-Day Food Records and the Food Frequency Questionnaire. Nutrition in Clinical Practice, 4, 142-148.

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