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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Editorial Board Member: Gillery, Philippe / Kazmierczak, Steven / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Schlattmann, Peter / Whitfield, John B.

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

Valentina Paracchini1 / Paola Pedotti2 / Sara Raimondi3 / Seymour Garte4 / H. Leon Bradlow5 / Daniel W. Sepkovic6 / Emanuela Taioli7

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Corresponding author: Emanuela Taioli, MD PhD, Molecular and Genetic Epidemiology Unit, Fondazione Ospedale Policlinico IRCCS, Palazzina Bertarelli, Via Pace 9, 20122 Milano, Italy Phone/Fax: +39-02-55034055,

Citation Information: Clinical Chemical Laboratory Medicine. Volume 43, Issue 7, Pages 702–706, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2005.119, July 2005

Publication History

Received:
April 19, 2005
Accepted:
April 25, 2005

Abstract

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.

Keywords: chemoprevention; epidemiology; estrogen metabolism; transitional study

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