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Do Urinary Estrogen Metabolites Reflect the Differences in Breast Cancer Risk between Singapore Chinese and United States African-American and White Women?¹

Department of Preventive Medicine [G. U., M. W., B. E. H., K. M., M. C. Y.], University of Southern California/Norris Comprehensive Cancer Center and Department of Obstetrics and Gynecology, University of Southern California/Los Angeles County Women’s Hospital [F. Z. S., E. G.], Los Angeles, California 90089; Cancer Etiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii 96813 [L. N. K.]; and Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore 117597 [H-P. L., A. S.]

Breast cancer risk is substantially lower in Singapore than in women from the United States. Part of the risk discrepancy is probably explained by differences in the production of endogenous estrogens, but differences in the pathway by which estrogen is metabolized may also play a role. We undertook a study to determine whether the ratio of urinary 2-hydroxyestrone (2OHE₁):16-hydroxyestrone (16-OHE₁) was higher in Singapore Chinese than in a group of United States (predominantly African-American) women living in Los Angeles. We also wanted to determine whether any difference in estrogen metabolite ratio between these two groups of women was greater than that in estrone (E₁), estradiol (E₂) and estriol (E₃). The participants in this study were randomly selected healthy, non-estrogen using women participating in the Singapore Chinese Health Study (n = 67) or the Hawaii/Los Angeles Multiethnic Cohort Study (n = 58). After adjusting for age and age at menopause, mean urinary 2-OHE₁ was only 23% (P = 0.03) higher in Singapore Chinese than in United States women, and there were no statistically significant differences in 16-OHE₁ levels or in the ratio of 2-OHE₁:16-OHE₁ between the two groups. The adjusted mean 2-OHE₁:16-OHE₁ ratio was 1.63 in Singapore Chinese and 1.48 in United States women (P = 0.41). In contrast, the adjusted mean values of E1, E2, and E3 were 162% (P < 0.0001), 152% (P < 0.0001), and 92% (P = 0.0009) higher, respectively, in United States women than in Singapore Chinese women. Our study suggests that urinary E1, E2, and E3 reflect the differences in breast cancer risk between Singapore Chinese and United States women to a stronger degree than the estrogen metabolites 2OHE₁ and 16-OHE₁ or the ratio of 2OHE₁:16-OHE_1.

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