Estrogen Metabolites, Conjugates, and DNA Adducts: Possible Biomarkers for Risk of Breast, Prostate, and Other Human Cancers

Abstract

Publisher Summary The chapter discusses that the identification and quantification of estrogen metabolites, conjugates, and depurinating DNA adducts in human specimens could provide early diagnostic tools for determining the risk of developing breast, prostate, and other human cancers. The analyses of estrogens, catechol estrogens, estrogen metabolites and conjugates, and depurinating catechol estrogen-DNA adducts are presented in this chapter. Many types of markers are being evaluated to estimate risk of developing breast cancer. These include breast density; body mass index; expression of BRCA1 and/or BRCA2 gene; cytological changes in breast epithelial cells collected by ductal lavage; and levels of estrogens and androgens in serum, breast tissue, or nipple aspirate fluid. The best biomarkers need to be identified, but a number of estrogen metabolites, estrogen conjugates, and depurinating estrogen-DNA adducts are likely candidates. Ongoing comparisons of women with and without breast cancer will allow us to identify the most promising candidate biomarkers of susceptibility. The most useful biomarkers will be validated through prospective studies that follow development of breast cancer in selected populations of women. The chapter also discusses the mechanisms of tumor initiation by estrogens and metabolism of estrogens. The chapter also discusses the biomarkers for increased risk of developing estrogen-initiated cancer. In the future, analysis of small molecules such as estrogen metabolites, estrogen conjugates, and depurinating estrogen-DNA adducts as biomarkers can be accomplished by using liquid chromatography/mass spectrometry. This approach is being used now to analyze serum for a variety of small molecules, and it should also be very effective to analyze breast fluid.