title: Endogenous Estrogens, Estrogen Metabolites, and Breast Cancer Risk in Postmenopausal Chinese Women.
abstract: The role of estrogen metabolism in determining breast cancer risk and differences in breast cancer rates between high-incidence and low-incidence nations is poorly understood.
  
  
  
  We measured urinary concentrations of estradiol and estrone (parent estrogens) and 13 estrogen metabolites formed by irreversible hydroxylation at the C-2, C-4, or C-16 positions of the steroid ring in a nested case-control study of 399 postmenopausal invasive breast cancer case participants and 399 matched control participants from the population-based Shanghai Women's Health Study cohort. Odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by quartiles of metabolic pathway groups, pathway ratios, and individual estrogens/estrogen metabolites were estimated by multivariable conditional logistic regression. Urinary estrogen/estrogen metabolite measures were compared with those of postmenopausal non-hormone-using Asian Americans, a population with three-fold higher breast cancer incidence rates. All statistical tests were two-sided.
  
  
  
  Urinary concentrations of parent estrogens were strongly associated with breast cancer risk (ORQ4vsQ1 = 1.94, 95% CI = 1.21 to 3.12, Ptrend = .01). Of the pathway ratios, the 2-pathway:total estrogens/estrogen metabolites and 2-pathway:parent estrogens were inversely associated with risk (ORQ4vsQ1 = 0.57, 95% CI = 0.35 to 0.91, Ptrend = .03, and ORQ4vsQ1 = 0.61, 95% CI = 0.37 to 0.99, Ptrend = .04, respectively). After adjusting for parent estrogens, these associations remained clearly inverse but lost statistical significance (ORQ4vsQ1 = 0.65, 95% CI = 0.39 to 1.06, Ptrend = .12 and ORQ4vsQ1 = 0.76, 95% CI = 0.44 to 1.32, Ptrend = .28). The urinary concentration of all estrogens/estrogen metabolites combined in Asian American women was triple that in Shanghai women.
  
  
  
  Lower urinary parent estrogen concentrations and more extensive 2-hydroxylation were each associated with reduced postmenopausal breast cancer risk in a low-risk nation. Markedly higher total estrogen/estrogen metabolite concentrations in postmenopausal United States women (Asian Americans) than in Shanghai women may partly explain higher breast cancer rates in the United States.
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Steven C
authors.initials: SC
authors.lastname: Moore
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Charles E
authors.initials: CE
authors.lastname: Matthews
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Xiao
authors.initials: X
authors.lastname: Ou Shu
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Mitchell H
authors.initials: MH
authors.lastname: Gail
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Bu-Tian
authors.initials: BT
authors.lastname: Ji
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Wong-Ho
authors.initials: WH
authors.lastname: Chow
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Honglan
authors.initials: H
authors.lastname: Li
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Gong
authors.initials: G
authors.lastname: Yang
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: David
authors.initials: D
authors.lastname: Ruggieri
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Jennifer
authors.initials: J
authors.lastname: Boyd-Morin
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (SCM, CEM, KY, MHG, BTJ, NR, RNH, RGZ); Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN (XOS, QC, GY, WZ); Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD (XX); Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (HL, YTG); Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, TX (WHC); Information Management Services, Inc., Rockville, MD (DR, JBM).
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
mesh_terms: D000368:Aged; D001213:Asian; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000652:urine*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D004958:Estradiol / Q000652:urine*; D004967:Estrogens / Q000378:metabolism / Q000652:urine*; D004970:Estrone / Q000652:urine*; D005260:Female; D006801:Humans; D015994:Incidence; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D016017:Odds Ratio; D017698:Postmenopause; D014481:United States
chemical_list: D004967:Estrogens; D004970:Estrone; D004958:Estradiol