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Cytochrome P450 (CYP) is a multigene family of enzymes involved in important life functions; some of these genes are inducible and are implicated in the oxidative metabolic activation and detoxification of many endogenous and exogenous compounds.  CYP1B1  codes for an enzyme that catalyses the production of a 2- and 4-hydroxyl group in estrone and estradiol, while  CYP1A1  catalyzes the 2-hydroxylation of estradiol in endometrium. The two genes were evaluated in a cohort of 150 subjects: African-American women had significantly lower 2-hydroxyl estrone/16-hydroxyl estrone (2-OHE1/16-OHE1) urinary metabolite ratios than Caucasian women (2.06±1.05 vs. 1.43±0.56; p=0.0002). A common polymorphism in the  CYP1B1  gene (leucine to valineat codon 432) was associated with changes in urinary estrogen levels: both Caucasian and African-American women carrying the variant allele showed higher urinary metabolite ratios than women with the wild-type allele. No effect of the  CYP1A1  MspI was observed. The 4-OHE1/2-OHE1 ratio was lower in subjects carrying the variant allele (Leu). The percentage change in 2-OHE1/16-OHE1 urinary ratio after indole treatment was significant in both Caucasian and African-American women carrying the wild-type  CYP1B1  genotype, although it was more evident in African-Americans than in Caucasians. These results suggest that the Leu/Val CYP1B1 polymorphism may modify estradiol metabolism.

A common CYP1B1 polymorphism is associated with 2-OHE1/16-OHE1 urinary estrone ratio