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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/4794

Title: Cytochrome P450 1A2 (CYP1A2) activity, mammographic density, and oxidative stress: a cross-sectional study
Authors: Hong, Chi-Chen,
Tang, Bing-Kou,
Rao, Venketeshwer,
Agarwal, Sanjiv,
Martin, Lisa,
Tritchler, David,
Yaffe, Martin,
Boyd, Norman F, boyd_at_uhnres.utoronto.ca
Keywords: caffeine metabolic ratio
malondialdehyde deoxyguanosine adducts
mammographic density
Issue Date: 7-May-2004
Publisher: BioMed Central Ltd.
Citation: Breast Cancer Res 2004(7 May); 6(4): R338-R351
Abstract: INTRODUCTION: Mammographically dense breast tissue is a strong predictor of breast cancer risk, and is influenced by both mitogens and mutagens. One enzyme that is able to affect both the mitogenic and mutagenic characteristics of estrogens is cytochrome P450 1A2 (CYP1A2), which is principally responsible for the metabolism of 17beta-estradiol. METHODS: In a cross-sectional study of 146 premenopausal and 149 postmenopausal women, we examined the relationships between CYP1A2 activity, malondialdehyde (MDA) levels, and mammographic density. In vivo CYP1A2 activity was assessed by measuring caffeine metabolites in urine. Levels of serum and urinary MDA, and MDA-deoxyguanosine adducts in DNA were measured. Mammograms were digitized and measured using a computer-assisted method. RESULTS: CYP1A2 activity in postmenopausal women, but not in premenopausal women, was positively associated with mammographic density, suggesting that increased CYP1A2 activity after the menopause is a risk factor for breast cancer. In premenopausal women, but not in postmenopausal women, CYP1A2 activity was positively associated with serum and urinary MDA levels; there was also some evidence that CYP1A2 activity was more positively associated with percentage breast density when MDA levels were high, and more negatively associated with percentage breast density when MDA levels were low. CONCLUSION: These findings provide further evidence that variation in the activity level of enzymes involved in estrogen metabolism is related to levels of mammographic density and potentially to breast cancer risk.
Description: Conclusion: Results from the present study suggest that CYP1A2 activity activity is related to mammographic density levels and oxidative stress, but that the nature of the relationship depends on menopausal status. These findings provide further evidence that variation in the level of activity of enzymes involved in estrogen metabolism is related to breast density levels and potentially breast cancer risk.
URI: http://hdl.handle.net/1807/4794
Appears in Collections:Epidemiology and Prevention

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