Relative imbalances in estrogen metabolism and conjugation in breast tissue of women with carcinoma: potential biomarkers of susceptibility to cancer.
Exposure to estrogens has been associated with an increased risk of developing breast cancer. Breast biopsy tissues from 49 women without breast cancer (controls) and 28 with breast carcinoma (cases) were analyzed by HPLC with electrochemical detection for 31 estrogen metabolites and catechol estrogen quinone-glutathione conjugates. The levels of estrone and estradiol were higher in cases. More 2-catechol estrogen (CE) than 4-CE was observed in controls, but the 4-CE were three times higher than 2-CE in cases. In addition, the 4-CE were nearly four times higher in cases than in controls. Less O-methylation was observed for the CE in cases. The level of catechol estrogen quinone conjugates in cases was three times that in controls, suggesting in the cases a higher probability for the quinones to react with DNA and generate mutations that may initiate cancer. The levels of 4-CE and quinone conjugates were highly significant predictors of breast cancer. These results suggest that some catechol estrogen metabolites and conjugates could serve as biomarkers to predict risk of breast cancer.
Rogan
Eleanor G
EG
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha 68198-6805, USA. egrogan@unmc.edu
Badawi
Alaa F
AF
Devanesan
Prabu D
PD
Meza
Jane L
JL
Edney
James A
JA
West
William W
WW
Higginbotham
Sheila M
SM
Cavalieri
Ercole L
EL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D008745:Methylation; D008875:Middle Aged
D014408:Biomarkers, Tumor; D004967:Estrogens