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Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women.
Cancer Res 2012; 72(3):696-706CR

Abstract

Endogenous 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.

Authors+Show Affiliations

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. heather.eliassen@channing.harvard.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

22144471

Citation

Eliassen, A Heather, et al. "Urinary Estrogens and Estrogen Metabolites and Subsequent Risk of Breast Cancer Among Premenopausal Women." Cancer Research, vol. 72, no. 3, 2012, pp. 696-706.
Eliassen AH, Spiegelman D, Xu X, et al. Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women. Cancer Res. 2012;72(3):696-706.
Eliassen, A. H., Spiegelman, D., Xu, X., Keefer, L. K., Veenstra, T. D., Barbieri, R. L., ... Ziegler, R. G. (2012). Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women. Cancer Research, 72(3), pp. 696-706. doi:10.1158/0008-5472.CAN-11-2507.
Eliassen AH, et al. Urinary Estrogens and Estrogen Metabolites and Subsequent Risk of Breast Cancer Among Premenopausal Women. Cancer Res. 2012 Feb 1;72(3):696-706. PubMed PMID: 22144471.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women. AU - Eliassen,A Heather, AU - Spiegelman,Donna, AU - Xu,Xia, AU - Keefer,Larry K, AU - Veenstra,Timothy D, AU - Barbieri,Robert L, AU - Willett,Walter C, AU - Hankinson,Susan E, AU - Ziegler,Regina G, Y1 - 2011/12/05/ PY - 2011/12/7/entrez PY - 2011/12/7/pubmed PY - 2012/3/31/medline SP - 696 EP - 706 JF - Cancer research JO - Cancer Res. VL - 72 IS - 3 N2 - Endogenous 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. SN - 1538-7445 UR - https://www.unboundmedicine.com/medline/citation/22144471/Urinary_estrogens_and_estrogen_metabolites_and_subsequent_risk_of_breast_cancer_among_premenopausal_women_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=22144471 DB - PRIME DP - Unbound Medicine ER -