Carcinogenesis Advance Access published online on March 28, 2003
Carcinogenesis, doi:10.1093/carcin/bgg047
© 2003 by Oxford University Press
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CARCINOGENESIS
1 The Jubileum Institute, Department of Oncology, Lund University Hospital, Sweden
Received 9 April 2002
; revised 5 March 2003
; accepted 8 March 2003
Studies of circulating estrogen levels in relation to premenopausal breast cancer risk have yielded inconsistent results. Various estrogen metabolites might affect the risk differently. Estradiol metabolism occurs primarily via two mutually exclusive pathways, yielding 2-hydroxyestrone (2OHE) and 16
Predictors of the plasma ratio of 2-hydroxyestrone to 16
-hydroxyestrone among premenopausal, nulliparous women from four ethnic groups
2 Immuna Care Corporation, Bethlehem, PA, USA
3 The David and Alice Institute for Research, Hackensack University Medical Center, 30 Prospect Ave, Hackensack, NJ, and Department of Medicine, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
4 Centre for Research in Women's Health, Sunnybrook and Women's College Hospital, Toronto, Canada
-hydroxyestrone (16OHE). Most, but not all, studies have found that a relatively high 2OHE/16OHE ratio is associated with a low breast cancer risk. Our objective was to determine if the 2OHE/16OHE ratio in plasma correlates with suspected breast cancer risk factors and other lifestyle factors such as ethnicity, body size, age at menarche, oral contraceptive use, smoking, vegetarian diet, coffee and alcohol consumption in 513 nulliparous women, aged 17 to 35. Oral contraceptive users had significantly lower 2OHE/16OHE ratios than non-pill-users (p = 10-21). Among women who were not using oral contraceptives, the median 2OHE/16OHE ratio in plasma was similar for white, black, Indian-Pakistani and Asian women, after adjustment for age and menstrual cycle phase. Among oral contraceptive users, Asian women had significantly lower 2OHE/16OHE ratios than white women, and this result remained after adjustment for age and day of menstrual cycle. Daily coffee consumption was significantly positively correlated with 2OHE/16OHE ratios (rs = 0.18; p = 0.002), only among non-pill-users. Our findings suggest that the plasma 2OHE/16OHE ratio is associated with constitutional factors and with modifiable lifestyle factors. The reported elevated risk of early-onset breast cancer among young oral contraceptive users could be mediated in part through altered estrogen metabolism induced by synthetic estrogens and progestins.
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