Environmental Health Perspectives 105, Supplement 3, March 1997

A Pilot Study of Urinary Estrogen Metabolites (16alpha-OHE1 and 2-OHE1) in Postmenopausal Women with and without Breast Cancer

Giske Ursin,1 Stephanie London,1,2 Frank Z. Stanczyk,3 Elisabet Gentzschein,3 Annlia Paganini-Hill,1 Ronald K. Ross,1 and Malcolm C. Pike1

1Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California; 2National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina; 3Department of Obstetrics and Gynecology, University of Southern California/Los Angeles County Women's Hospital, Los Angeles, California

Abstract

The two main pathways for metabolizing estrogen are via 16alpha-hydroxylation and 2-hydroxylation. The 16alpha-hydroxy metabolites are biologically active; the 2-hydroxy metabolites are not. It is suggested that women who metabolize a larger proportion of their endogenous estrogen via the 16alpha-hydroxy pathway may be at significantly elevated risk of breast cancer compared with women who metabolize proportionally more estrogen via the 2-hydroxy pathway. In particular, it is suggested that the ratio of urinary 2-hydroxyestrone (2-OHE1) to 16alpha-hydroxyestrone (16alpha-OHE1) is an index of reduced breast cancer risk. This pilot study compared this ratio in postmenopausal women diagnosed with breast cancer to those of healthy controls. Urinary concentrations of estrone (E1), 17ß-estradiol (E2) and estriol (E3) were also quantified. White women who were subjects in a previous breast cancer case-control study at our institution were eligible for inclusion. All participants provided a sample of their first morning urine. The results from the first 25 cases and 23 controls are presented here. The ratio of 2-OHE1 to 16alpha-OHE1 was 12% lower in the cases (p=0.58). However, urinary E1 was 30% higher (p=0.10), E2 was 58% higher (p=0.07), E3 was 15% higher (p=0.48), and the sum of E1, E2, and E3 was 22% higher (p=0.16) in the cases. These preliminary results do not support the hypothesis that the ratio of the two hydroxylation metabolites (2-OHE1/16alpha-OHE1) is an important risk factor for breast cancer or that it is a better predictor of breast cancer risk than levels of E1, E2 and E3 measured in urine. -- Environ Health Perspect 105(Suppl 3):601-605 (1997)

Key words: estrogen metabolism, 16alpha-hydroxyestrone, 2-hydroxyestrone, breast cancer, urinary estrogen metabolites

This paper was presented in part at the Workshop on Hormones, Hormone Metabolism, Environment, and Breast Cancer held 28-29 September 1995 in New Orleans, Louisiana. Manuscript received at EHP 6 June 1996; manuscript accepted 29 August 1996.
This project was supported by the following grants: National Institutes of Health 5 P01 CA 17054, U.S. Army Medical Research and Materiel Command 17-94-J-4289, DAMD17-94-J-4049 (G. Ursin) and by the California Department of Health Services through the California Public Health Foundation, as part of its statewide cancer reporting program mandated by Health and Safety Code Sections 210 and 211.3. The ideas and opinions expressed herein are those of the authors, and no endorsement by the State of California Department of Health Services or the California Public Health Foundation is intended or should be inferred. S. London was supported in part by a Research Career Development Award from Stop Cancer.
Address correspondence to Dr. G. Ursin, Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Ave, MS #44, Suite 4408, Los Angeles, CA 90033-0800. Telephone: (213) 764-0423. Fax: (213) 764-0142. E-mail: :gursin@hsc.nsc.edu
Abbreviations used: E1, estrone; E2, 17ß-estradiol; E3, estriol; EIA, enzyme immunoassay; HPLC, high-performance liquid chromatography; 2-OHE1, 2-hydroxyestrone; 16alpha-OHE1, 16alpha-hydroxyestrone; RIA, radioimmunoassay.
[Table of Contents] [Full Article]

Last Update: April 10, 1997 r