Journal Article

Predictors of the plasma ratio of 2-hydroxyestrone to 16α-hydroxyestrone among pre-menopausal, nulliparous women from four ethnic groups

H. Jernström, T.L. Klug, D.W. Sepkovic, H.L. Bradlow and S.A. Narod

in Carcinogenesis

Volume 24, issue 5, pages 991-1005
Published in print May 2003 | ISSN: 0143-3334
Published online May 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg047
Predictors of the plasma ratio of 2-hydroxyestrone to 16α-hydroxyestrone among pre-menopausal, nulliparous women from four ethnic groups

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Studies of circulating estrogen levels in relation to pre-menopausal 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 (2-OHE) and 16α-hydroxyestrone (16α-OHE). Most, but not all, studies have found that a relatively high 2-OHE/16α-OHE ratio is associated with a low breast cancer risk. Our objective was to determine if the 2-OHE/16α-OHE 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 17–35. Oral contraceptive users had significantly lower 2-OHE/16α-OHE ratios than pill non-users (P = 10−21). Among women who were not using oral contraceptives, the median 2-OHE/16α-OHE 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 2-OHE/16α-OHE 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 2-OHE/16α-OHE ratios (rs = 0.18, P = 0.002) only among pill non-users. Our findings suggest that the plasma 2-OHE/16α-OHE 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.

Keywords: BMI, body mass index; 16α-OHE; 16α-hydroxyestrone; 2-OHE, 2-hydroxyestrone.

Journal Article.  8124 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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