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Vol. 28 Issue 1 (January-March)

Urinary estrogen metabolites and breast cancer: a combined analysis of individual level data

Urinary estrogen metabolites and breast cancer: a combined analysis of individual level data

Int J Biol Markers 2013; 28(1): 3 - 16

Article Type: ORIGINAL ARTICLE

DOI:10.5301/JBM.2012.9353

Authors

Cher M. Dallal, Roslyn A. Stone, Jane A. Cauley, Roberta B. Ness, Victor G. Vogel, Ian S. Fentiman, Jay H. Fowke, Vittorio Krogh, Steffen Loft, Elaine N. Meilahn, Paola Muti, Anja Olsen, Kim Overvad, Sabina Sieri, Anne Tjønneland, Giske Ursin, Anja Wellejus, Emanuela Taioli

Abstract

Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1), and their ratio (2:16α-OHE1) in relation to breast cancer risk. 
Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status.
Results: Higher premenopausal 2:16α-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16α-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvsI=0.93; 95% CI: 0.65-1.33); however, the association between 2-OHE1 and risk varied by body mass index (p-interaction=0.003). 
Conclusions: Premenopausal urinary 2:16α-OHE1 may play a role in breast carcinogenesis; however, larger studies are needed. Our findings do not support reduced breast cancer risk with higher postmenopausal 2:16α-OHE1 overall, although obesity may modify associations with 2-OHE1.

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Authors

  • Dallal, Cher M. [PubMed] [Google Scholar]
    Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania - USA
  • Stone, Roslyn A. [PubMed] [Google Scholar]
    Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania - USA
  • Cauley, Jane A. [PubMed] [Google Scholar]
    Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania - USA
  • Ness, Roberta B. [PubMed] [Google Scholar]
    The University of Texas School of Public Health, Houston, Texas - USA
  • Vogel, Victor G. [PubMed] [Google Scholar]
    Geisinger Cancer Institute, Geisinger Medical Center, Danville, Pennsylvania - USA
  • Fentiman, Ian S. [PubMed] [Google Scholar]
    Research Oncology, Guy’s Hospital, London - England
  • Fowke, Jay H. [PubMed] [Google Scholar]
    Division of Epidemiology, Vanderbilt University Medical Center, Nashville, Tennessee - USA
  • Krogh, Vittorio [PubMed] [Google Scholar]
    Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan - Italy
  • Loft, Steffen [PubMed] [Google Scholar]
    Department of Public Health, University of Copenhagen, Copenhagen - Denmark
  • Meilahn, Elaine N. [PubMed] [Google Scholar]
    Marion DuPont Scott Equine Medical Center, College of Veterinary Medicine, Virginia Polytechnic Institute, Leesburg, Virginia - USA
  • Muti, Paola [PubMed] [Google Scholar]
    Italian National Cancer Institute “Regina Elena”, Rome - Italy
  • Olsen, Anja [PubMed] [Google Scholar]
    Unit of Diet, Genes, and Environment, the Danish Cancer Society Research Center, Copenhagen - Denmark
  • Overvad, Kim [PubMed] [Google Scholar]
    Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus - Denmark
  • Sieri, Sabina [PubMed] [Google Scholar]
    Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan - Italy
  • Tjønneland, Anne [PubMed] [Google Scholar]
    Unit of Diet, Genes, and Environment, the Danish Cancer Society Research Center, Copenhagen - Denmark
  • Ursin, Giske [PubMed] [Google Scholar]
    Department of Preventive Medicine, University of Southern California, Los Angeles, California - USA
  • Wellejus, Anja [PubMed] [Google Scholar]
    Department of Public Health, University of Copenhagen, Copenhagen - Denmark
  • Taioli, Emanuela [PubMed] [Google Scholar]
    Department of Population Health, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York - USA

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