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Urinary Estrogen Metabolites and Their Ratio among Asian American Women

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; ² Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; ³ Etiology Program, Cancer Research Center, University of Hawaii, Honolulu, Hawaii; ⁴ Northern California Cancer Center, Union City, California; and ⁵ Alice and David Jurist Institute for Research, Hackensack University Medical Center, Hackensack, New Jersey

Requests for reprints: Roni T. Falk, Environmental Epidemiology Branch, National Cancer Institute, 6120 Executive Boulevard, MSC-7234, Suite 7070, Bethesda, MD 20892. Phone: 301-435-3982. E-mail: falkr{at}exchange.nih.gov

Controversy persists regarding the role of a low ratio of 2-hydroxyestone (2-OHE₁)/16-hydroxyestrone (16-OHE₁) as a potential estrogen metabolism marker of increased risk for breast cancer. Most of the evidence has been provided by case-control studies, where tumor effects on hormone metabolism are not known. Studies in populations at various risk of breast cancer are not consistent, with some suggesting that levels of the ratio may be altered by changes in diet and exercise. We studied Asian American women participating as controls in a case-control study of breast cancer in which migration history—a composite of the subject's place of birth, type of residence in Asia (urban or rural), length of time living in the West, and grandparents' place of birth—was associated with a 6-fold risk gradient that paralleled the historical differences in incidence rates between the United States and Asian countries. This population offered the possibility to address whether the ratio of 2-OHE₁:16-OHE₁ differs according to recognized breast cancer risk factors, including migration history. Overnight 12-hour urines were obtained from 368 premenopausal and 143 naturally postmenopausal women of Chinese, Japanese, or Filipino descent who donated urines between 1985 and 1988. The estrogen metabolites 2-OHE₁ and 16-OHE₁ were measured with an ELISA kit and adjusted for creatinine levels. In each ethnic group, the ratio of 2-OHE₁:16-OHE₁ was consistently lower in women born in the West than in those who had migrated from Asia. For premenopausal women, the ratio declined 20% due to lower levels of 2-OHE₁. Among postmenopausal women, the ratio was 23% lower in those born in the West, but no consistent patterns based on place of birth were observed for either 2-OHE₁ or 16-OHE₁. The ratio did not vary with most recognized breast cancer risk factors, except for lower metabolite ratios in women with a younger age at first birth and more children, which runs contrary to the hypothesis, because both characteristics reduce breast cancer risk. Our study suggests that the ratio of 2-OHE₁:16-OHE₁ may be a marker for lifestyle influences on estrogen metabolism associated with westernization.

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