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Investigation of the cumulative body burden of estrogen-3,4-quinone in breast cancer patients and controls using albumin adducts as biomarkers.

Toxicol Lett. 2013 Feb 16;

Authors: Lin C, Chen DR, Hsieh WC, Yu WF, Lin CC, Ko MH, Juan CH, Tsuang BJ, Lin PH


Both 17β-estradiol-2,3-quinone (E(2)-2,3-Q) and 17β-estradiol-3,4-quinone (E(2)-3,4-Q)are reactive metabolites of estrogen. Elevation of E(2)-3,4-Q to E(2)-2,3-Q ratio is thought to be an important indicator of estrogen-induced carcinogenesis. Our current study compared the cumulative body burden of these estrogen quinones in serum samples taken from Taiwanese women with breast cancer (n=152) vs healthy controls (n=75) by using albumin (Alb) adducts as biomarkers. Results clearly demonstrated the presence of cysteinyl adducts of E(2)-2,3-Q-4-S-Alb and E(2)-3,4-Q-2-S-Alb in all study population at levels ranging from 61.7-1330 and 66.6-1590pmol/g, respectively. Correlation coefficient between E(2)-2,3-Q-4-S-Alb and E(2)-3,4-Q-2-S-Alb was 0.610 for controls and 0.767 for breast cancer patients (p<0.001). We also noticed that in premenopausal subjects with body mass index (BMI) less than 27, background levels of E(2)-3,4-Q-2-S-Alb was inversely proportional to BMI with about 25% increase in E(2)-3,4-Q-2-S-Alb per 5kg/m(2) decrease in BMI (p<0.001). In addition, we confirmed that mean levels of E(2)-3,4-Q-2-S-Alb in breast cancer patients were ∼5 fold greater than in those of controls (p<0.001). Overall, this evidence suggests that disparity in estrogen disposition and the subsequent elevation of cumulative body burden of E(2)-3,4-Q may play a role in the development of breast cancer.

PMID: 23422263 [PubMed - as supplied by publisher]