Abstract
BackgroundAn important aspect of the link between estrogen and breast cancer is whether urinary estrogen levels are representative of the intra-tissue levels of bioavailable estrogens.MethodsThis study compares 15 estrogen and estrogen metabolite levels in breast tissue and urine of 9 women with primary breast cancer using a quantitative liquid chromatography-mass spectrometry method.ResultsThe average levels of estrogens (estrone, 17 beta-estradiol) were significantly higher in breast tissue than in urine. Both the 2 and the 16-hydroxylation pathways were less represented in breast tissue than urine; no components of the 4-hydroxypathway were detected in breast tissue, while 4-hydroxyestrone was measured in urine. However, the 2/16 ratio was similar in urine and breast tissue. Women carrying the variant CYP1B1 genotype (Leu/Val and Val/Val) showed significantly lower overall estrogen metabolite, estrogen, and 16-hydroxylation pathway levels in breast tissue in comparison to women carrying the wild type genotype. No effect of the CYP1B1 polymorphism was observed in urinary metabolites.ConclusionsThe urinary 2/16 ratio seems a good approximation of the ratio observed in breast tissue. Metabolic genes may have an important role in the estrogen metabolism locally in tissues where the gene is expressed, a role that is not readily observable when urinary measurements are performed.
Highlights
An important aspect of the link between estrogen and breast cancer is whether urinary estrogen levels are representative of the intra-tissue levels of bioavailable estrogens
Limited research has been conducted in humans on the effects on estrogen metabolites of metabolic gene polymorphisms involved in estrogen metabolism, a common CYP1B1 polymorphism (Val432Leu) has been shown to influence the 2/16 ratio in healthy women, possibly by catalyzing the formation of the 2 hydroxyl group [11]
In a small sample of women, that the sum of the estrogen metabolite levels in urine do reflect that formed in the target organ human breast tissue, while this is much less true for most individual metabolites
Summary
An important aspect of the link between estrogen and breast cancer is whether urinary estrogen levels are representative of the intra-tissue levels of bioavailable estrogens. Estrogen metabolites have been extensively studied as breast cancer risk factors This process involves an oxidative pathway, beginning with the conversion of estradiol to estrone, and continues through hydroxylation at sites C2, C4 or C-16 [6]. While the prevailing hypothesis suggests that a higher 2-OHE1 to 16a-OHE1 ratio would predict a lower breast cancer risk, the results have been inconsistent Methodological reasons such as the variability of estrogen levels and metabolism across the menstrual cycle, the effect of both genetic and environmental factors on estrogen production and metabolism, and the use of urine or serum measurements as surrogate markers of breast tissue estrogen metabolism, may be the basis of the varying results provided by the different studies
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