Comparison of estrogens and estrogen metabolites in human breast tissue and urine

Reprod Biol Endocrinol. 2010 Aug 2;8:93. doi: 10.1186/1477-7827-8-93.

Abstract

Background: 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.

Methods: This 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.

Results: The 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.

Conclusions: The 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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aryl Hydrocarbon Hydroxylases
  • Breast / metabolism*
  • Breast / pathology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / urine
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / urine
  • Case-Control Studies
  • Cytochrome P-450 CYP1B1
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Estradiol / metabolism*
  • Estradiol / urine*
  • Estrogens / metabolism*
  • Estrogens / urine*
  • Female
  • Gene Frequency
  • Humans
  • Leucine / genetics
  • Metabolic Networks and Pathways / genetics
  • Metabolic Networks and Pathways / physiology
  • Metabolome
  • Middle Aged
  • Polymorphism, Single Nucleotide / physiology
  • Valine / genetics

Substances

  • Estrogens
  • Estradiol
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • CYP1B1 protein, human
  • Cytochrome P-450 CYP1B1
  • Leucine
  • Valine