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Grant Details

Grant Number: 5R01CA106591-04 Interpret this number
Primary Investigator: Dai, Qi
Organization: Vanderbilt University
Project Title: Oxidative Stress, Antioxidants and Breast Cancer Risk
Fiscal Year: 2007
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Abstract

DESCRIPTION (provided by applicant): Substantial evidence from Iaboratory studies has indicated an important role of reactive oxygen species (ROS), produced by estrogen metabolism, in mammary carcinogenesis. This application is to evaluate whether the biomarker of systemic oxidative stress may be associated with breast cancer risk, whether antioxidant polyphenols, consumed in large quantities among Chinese women in Shanghai, may reduce the risk of breast cancer, particularly among those with a high exposure to ROS. To achieve these research goals, we propose to conduct a nested case-control study of 430 breast cancer cases and 860 individually matched controls within the cohort of the Shanghai Women's Health Study (RO1CA 70867), a population-based cohort study of approximately 75,000 Chinese women. In addition to in-person interviews, blood (or buccal cell) and urine samples were collected from 87.5% cohort members. For this proposed study, urinary level of total phenols will be assayed with Folin-Ciocalteu Phenol Reagent, urinary levels of polyphenol flavonols and flavanols will be determined using liquid chromatography photo-diode array electrospray mass spectrometry, urinary level of 2,3-dinor-5,6-dihydro-15-F2t-lsoP will be quantified by gas chromatography/negative ion chemical ionization mass spectrometry, blood levels of tocopherols and carotenoids will be analyzed using HPLC methods, and genotypes of the enzymes involved in ROS detoxification will be assayed using PCR-RFLP methods. The associations between these biomarkers and breast cancer risk will be evaluated. We also will perform statistical analyses to evaluate the joint effects or potential interactions of total phenols, flavonols and flavanols with soy isoflavonoids, antioxidant nutrients, genotypes of ROS detoxification enzymes and oxidative stress level in relation to breast cancer risk. The study population will be unique given the high intake levels of total phenols, flavonols, flavanols, isoflavonoids. Because questionnaire data and specimen collection, follow-up survey as well as assays for isoflavonoids are supported by the existing study, this project will be very cost-efficient. In addition, we will also be able to expand our study to a larger scale if the results are promising. Findings from this study will have important public health implications in the primary prevention of breast cancer.

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Publications

Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies.
Authors: Eliassen AH, Hendrickson SJ, Brinton LA, Buring JE, Campos H, Dai Q, Dorgan JF, Franke AA, Gao YT, Goodman MT, Hallmans G, Helzlsouer KJ, Hoffman-Bolton J, HultÚn K, Sesso HD, Sowell AL, Tamimi RM, Toniolo P, Wilkens LR, Winkvist A, Zeleniuch-Jacquotte A, Zheng W, Hankinson SE
Source: J Natl Cancer Inst, 2012 Dec 19;104(24), p. 1905-16.
EPub date: 2012 Dec 6.
PMID: 23221879
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Major metabolite of F2-isoprostane in urine may be a more sensitive biomarker of oxidative stress than isoprostane itself.
Authors: Dorjgochoo T, Gao YT, Chow WH, Shu XO, Yang G, Cai Q, Rothman N, Cai H, Li H, Deng X, Franke A, Roberts LJ, Milne G, Zheng W, Dai Q
Source: Am J Clin Nutr, 2012 Aug;96(2), p. 405-14.
EPub date: 2012 Jul 3.
PMID: 22760572
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Urinary polyphenols, glutathione S-transferases copy number variation, and breast cancer risk: results from the Shanghai women's health study.
Authors: Luo J, Gao YT, Chow WH, Shu XO, Li H, Yang G, Cai Q, Li G, Rothman N, Cai H, Shrubsole MJ, Franke AA, Zheng W, Dai Q
Source: Mol Carcinog, 2012 May;51(5), p. 379-88.
EPub date: 2011 May 6.
PMID: 21557334
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Low plasma coenzyme Q(10) levels and breast cancer risk in Chinese women.
Authors: Cooney RV, Dai Q, Gao YT, Chow WH, Franke AA, Shu XO, Li H, Ji B, Cai Q, Chai W, Zheng W
Source: Cancer Epidemiol Biomarkers Prev, 2011 Jun;20(6), p. 1124-30.
EPub date: 2011 Apr 5.
PMID: 21467235
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Obesity, age, and oxidative stress in middle-aged and older women.
Authors: Dorjgochoo T, Gao YT, Chow WH, Shu XO, Yang G, Cai Q, Rothman N, Cai H, Li H, Deng X, Shrubsole MJ, Murff H, Milne G, Zheng W, Dai Q
Source: Antioxid Redox Signal, 2011 Jun 15;14(12), p. 2453-60.
EPub date: 2011 Mar 21.
PMID: 21043829
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F2-isoprostanes and Metabolite, and Breast Cancer Risk.
Authors: Dai Q, Zhu X
Source: N Am J Med Sci (Boston), 2009 Jul;2(3), p. 106-108.
PMID: 20648235
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Is green tea drinking associated with a later onset of breast cancer?
Authors: Dai Q, Shu XO, Li H, Yang G, Shrubsole MJ, Cai H, Ji B, Wen W, Franke A, Gao YT, Zheng W
Source: Ann Epidemiol, 2010 Jan;20(1), p. 74-81.
PMID: 20006278
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Urinary polyphenols and breast cancer risk: results from the Shanghai Women's Health Study.
Authors: Luo J, Gao YT, Chow WH, Shu XO, Li H, Yang G, Cai Q, Rothman N, Cai H, Shrubsole MJ, Franke AA, Zheng W, Dai Q
Source: Breast Cancer Res Treat, 2010 Apr;120(3), p. 693-702.
EPub date: 2009 Aug 4.
PMID: 19653095
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Oxidative stress, obesity, and breast cancer risk: results from the Shanghai Women's Health Study.
Authors: Dai Q, Gao YT, Shu XO, Yang G, Milne G, Cai Q, Wen W, Rothman N, Cai H, Li H, Xiang Y, Chow WH, Zheng W
Source: J Clin Oncol, 2009 May 20;27(15), p. 2482-8.
EPub date: 2009 Apr 20.
PMID: 19380446
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Plasma carotenoids, tocopherols, retinol and breast cancer risk: results from the Shanghai Women Health Study (SWHS).
Authors: Dorjgochoo T, Gao YT, Chow WH, Shu XO, Li H, Yang G, Cai Q, Rothman N, Cai H, Franke AA, Zheng W, Dai Q
Source: Breast Cancer Res Treat, 2009 Sep;117(2), p. 381-9.
EPub date: 2008 Dec 20.
PMID: 19096929
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