Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women
Eliassen, A. Heather
Keefer, Larry K.
Veenstra, Timothy D.
Barbieri, Robert L.
Willett, Walter C.::94559ea206eef8a8844fc5b80654fa5b::600
Hankinson, Susan E.
Ziegler, Regina G.
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CitationEliassen, A. H., D. Spiegelman, X. Xu, L. K. Keefer, T. D. Veenstra, R. L. Barbieri, W. C. Willett, S. E. Hankinson, and R. G. Ziegler. 2011. “Urinary Estrogens and Estrogen Metabolites and Subsequent Risk of Breast Cancer among Premenopausal Women.” Cancer Research 72 (3): 696–706. https://doi.org/10.1158/0008-5472.can-11-2507.
AbstractEndogenous estrogens and estrogen metabolism are hypothesized to be associated with premenopausal breast cancer risk but evidence is limited. We examined 15 urinary estrogens/estrogen metabolites and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II (NHSII). From 1996 to 1999, urine was collected from 18,521 women during the mid-luteal menstrual phase. Breast cancer cases (N = 247) diagnosed between collection and June 2005 were matched to two controls each (N = 485). Urinary estrogen metabolites were measured by liquid chromatography-tandem mass spectrometry and adjusted for creatinine level. Relative risks (RR) and 95% confidence intervals (CI) were estimated by multivariate conditional logistic regression. Higher urinary estrone and estradiol levels were strongly significantly associated with lower risk (top vs. bottom quartile RR: estrone = 0.52; 95% CI, 0.30-0.88; estradiol = 0.51; 95% CI, 0.30-0.86). Generally inverse, although nonsignificant, patterns also were observed with 2- and 4-hydroxylation pathway estrogen metabolites. Inverse associations generally were not observed with 16-pathway estrogen metabolites and a significant positive association was observed with 17-epiestriol (top vs. bottom quartile RR 1.74; 95% CI, 1.08-2.81; P-trend = 0.01). In addition, there was a significant increased risk with higher 16-pathway/parent estrogen metabolite ratio (comparable RR 1.61; 95% CI, 0.99-2.62; P-trend = 0.04). Other pathway ratios were not significantly associated with risk except parent estrogen metabolites/non-parent estrogen metabolites (comparable RR 0.58; 95% CI, 0.35-0.96; P-trend = 0.03). These data suggest that most mid-luteal urinary estrogen metabolite concentrations are not positively associated with breast cancer risk among premenopausal women. The inverse associations with parent estrogen metabolites and the parent estrogen metabolite/non-parent estrogen metabolite ratio suggest that women with higher urinary excretion of parent estrogens are at lower risk. Cancer Res; 72(3); 696-706.
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