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Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women.

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.

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  • 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.edu

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    Source

    Cancer research 72:3 2012 Feb 01 pg 696-706

    MeSH

    Adult
    Breast Neoplasms
    Case-Control Studies
    Cell Transformation, Neoplastic
    Chromatography, Liquid
    Estriol
    Estrogens
    Estrone
    Female
    Humans
    Logistic Models
    Middle Aged
    Molecular Structure
    Multivariate Analysis
    Premenopause
    Risk Assessment
    Risk Factors
    Tandem Mass Spectrometry

    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 -