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Grant Details

Grant Number: 5R01CA070264-04 Interpret this number
Primary Investigator: Li, Donghui
Organization: University Of Texas Md Anderson Can Ctr
Project Title: DNA Adduct, P53 Mutation, and Etiology of Breast Cancer
Fiscal Year: 2000
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Abstract

Breast cancer affects more women than any other cancers in the western hemisphere. The etiology of the majority of human breast cancers is unknown. To identify the etiologic agents and risk factors involved breast cancers, this project will test the hypothesis that environmental carcinogen exposures may contribute to human breast cancers. DNA adducts will be measured and compared in surgical specimens of breast tissue from 150 breast cancer patients and 75 non-cancer controls by the 32P-postlabeling method. DNA adduct profiles will be compared between cases and controls, and between subgroups among cases, e.g. smokers versus non-smokers and women consume a high fat diet versus those with a low fat diet. To explore the potential sources of exposure related to adducts detected in breast tissues, possible exposure will be assessed by epidemiologic approaches. Information on dietary history, smoking, occupation, and alcohol consumption will be obtained from each subject by a self-administered questionnaire. A 10 ml blood sample will be obtained from 50 cases to determine whether lymphocytes can be used as a surrogate. DNA adducts will be measure in lymphocytes and mammary epithelial cells exposed to a carcinogen in culture in 50 cases and 50 controls to determine whether sensitivity to carcinogen exposure is a risk factor for breast cancer. A major adduct which was detected in 40% of breast cancer patients but none of the controls will be identified by comparing with adduct profiles generated in microsomal reaction, cell culture, and tissue culture systems. Since DNA adduct formation and consequent gene mutation are believed to be the key events in chemical carcinogenesis this project will test the hypothesis that the frequency and spectrum of p53 gene mutation is related to adduct formation and may reflect exposure to specific etiologic agents. p53 mutation in tumors of the 150 cases will be determined by single strand conformation polymorphism assay and direct DNA sequencing. The mutation data will be evaluated in relation to the DNA adduct status and the epidemiologic information. These studies are designed to explore the role of environmental carcinogens in human breast cancer development and t define candidate carcinogens and their sources in the environment. Such information is important in identifying etiologic factors in human breast cancers and in finding new strategies for primary prevention of breast cancer

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Publications

Effect of dietary intake of phytoestrogens on estrogen receptor status in premenopausal women with breast cancer.
Authors: Touillaud M.S. , Pillow P.C. , Jakovljevic J. , Bondy M.L. , Singletary S.E. , Li D. , Chang S. .
Source: Nutrition and cancer, 2005; 51(2), p. 162-9.
PMID: 15860438
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Detection of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine-DNA adducts in normal breast tissues and risk of breast cancer.
Authors: Zhu J. , Chang P. , Bondy M.L. , Sahin A.A. , Singletary S.E. , Takahashi S. , Shirai T. , Li D. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2003 Sep; 12(9), p. 830-7.
PMID: 14504191
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Elevated luteinizing hormone in serum, breast cancer tissue, and normal breast tissue from breast cancer patients.
Authors: Silva E.G. , Mistry D. , Li D. , Kuerer H.M. , Atkinson E.N. , Lopez A.N. , Shannon R. , Hortobagyi G.N. .
Source: Breast cancer research and treatment, 2002 Nov; 76(2), p. 125-30.
PMID: 12452449
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Dietary intake of selected fatty acids, cholesterol and carotenoids and estrogen receptor status in premenopausal breast cancer patients.
Authors: Jakovljevic J. , Touillaud M.S. , Bondy M.L. , Singletary S.E. , Pillow P.C. , Chang S. .
Source: Breast cancer research and treatment, 2002 Sep; 75(1), p. 5-14.
PMID: 12500930
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Genetic and environmental determinants on tissue response to in vitro carcinogen exposure and risk of breast cancer.
Authors: Li D. , Walcott F.L. , Chang P. , Zhang W. , Zhu J. , Petrulis E. , Singletary S.E. , Sahin A.A. , Bondy M.L. .
Source: Cancer research, 2002-08-15; 62(16), p. 4566-70.
PMID: 12183407
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Aromatic DNA adducts and polymorphisms of CYP1A1, NAT2, and GSTM1 in breast cancer.
Authors: Firozi P.F. , Bondy M.L. , Sahin A.A. , Chang P. , Lukmanji F. , Singletary E.S. , Hassan M.M. , Li D. .
Source: Carcinogenesis, 2002 Feb; 23(2), p. 301-6.
PMID: 11872636
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Characterization of a major aromatic DNA adduct detected in human breast tissues.
Authors: Li D. , Wang M. , Firozi P.F. , Chang P. , Zhang W. , Baer-Dubowska W. , Moorthy B. , Vulimiri S.V. , Goth-Goldstein R. , Weyand E.H. , et al. .
Source: Environmental and molecular mutagenesis, 2002; 39(2-3), p. 193-200.
PMID: 11921189
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Adoptive T-cell therapy for the treatment of solid tumours.
Authors: Knutson K.L. , Almand B. , Mankoff D.A. , Schiffman K. , Disis M.L. .
Source: Expert opinion on biological therapy, 2002 Jan; 2(1), p. 55-66.
PMID: 11772340
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Sensitivity to benzo(a)pyrene diol-epoxide associated with risk of breast cancer in young women and modulation by glutathione S-transferase polymorphisms: a case-control study.
Authors: Xiong P. , Bondy M.L. , Li D. , Shen H. , Wang L.E. , Singletary S.E. , Spitz M.R. , Wei Q. .
Source: Cancer research, 2001-12-01; 61(23), p. 8465-9.
PMID: 11731429
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Oxidative DNA damage and 8-hydroxy-2-deoxyguanosine DNA glycosylase/apurinic lyase in human breast cancer.
Authors: Li D. , Zhang W. , Zhu J. , Chang P. , Sahin A. , Singletary E. , Bondy M. , Hazra T. , Mitra S. , Lau S.S. , et al. .
Source: Molecular carcinogenesis, 2001 Aug; 31(4), p. 214-23.
PMID: 11536371
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DNA adducts in normal tissue adjacent to breast cancer: a review.
Authors: Li D. , Zhang W. , Sahin A.A. , Hittelman W.N. .
Source: Cancer detection and prevention, 1999; 23(6), p. 454-62.
PMID: 10571655
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