Cytochrome P450 1A2 (CYP1A2) activity, mammographic density, and oxidative stress: a cross-sectional study.
BACKGROUND
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.


CONCLUSIONS
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.
Hong
Chi-Chen
CC
Division of Epidemiology and Statistics, Ontario Cancer Institute, Toronto, Ontario, Canada. chong@uhnres.utoronto.ca
Tang
Bing-Kou
BK
Rao
Venketeshwer
V
Agarwal
Sanjiv
S
Martin
Lisa
L
Tritchler
David
D
Yaffe
Martin
M
Boyd
Norman F
NF
D000328:Adult; D001940:Breast / Q000201:enzymology* / Q000473:pathology*; D001943:Breast Neoplasms / Q000473:pathology; D003430:Cross-Sectional Studies; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D008315:Malondialdehyde / Q000097:blood / Q000652:urine; D008327:Mammography; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D017698:Postmenopause / Q000097:blood / Q000378:metabolism; D017697:Premenopause / Q000097:blood / Q000378:metabolism; D012307:Risk Factors
D004958:Estradiol; D008315:Malondialdehyde; C089188:3-(2'-deoxyribofuranosyl)pyrimido(1,2-a)purin-10(3H)-one; D019388:Cytochrome P-450 CYP1A2; D003849:Deoxyguanosine