Ethnic differences in estrogen metabolism in healthy women.

The high incidence of breast cancer observed in young African-American women (7) and the apparent aggressiveness of the disease in this ethnic group (2) might be because of biologic differences, such as genetic susceptibility to environmental factors and/or hormonal levels. We have recently shown (3) that a polymorphism in the CYP1 Al gene, which is involved in estrogen metabolism, is significantly associated with breast cancer in African-American, but not in Caucasian, women. The endogenous metabolism of estrogens is primarily oxidative and involves hydroxylation of the steroid at either C2 (2-0HE1) or C16a (16a-0HEl). While the 2-OHE1 metabolites are essentially devoid of peripheral biologic activity, 16a-0HEl is an estrogen agonist (4,5). There is evidence of an inverse association between the 2-OHEl/16a-OHEl metabolite ratio and breast cancer risk (6). We present here the basal urinary estrogen metabolite ratio (as measured by an enzyme-linked immunosorbent assay method) in 33 healthy women aged 18-73 years (7). Women taking oral contraceptives or who were pregnant or lactating were excluded. African-American women had significantly lower 2-OHEl/16a-OHEl urinary metabolite ratios than did Caucasian women (Table 1). No effect of age, weight, smoking status, or CYP1A1 genotype was observed. The observed differences in the estrogen metabolite ratio between CauTable 1. Base-line ratios of urinary estrogen metabolites (2-OHE1/16a-OHE 1) according to ethnicity*