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

Abstract

Both 17 -estradiol-2,3-quinone (E2-2,3-Q) and 17 -estradiol-3,4-quinone (E2-3,4-Q) are reactivemetabolites of estrogen. Elevation of E2-3,4-Q to E2-2,3-Q ratio is thought to be an important indicatorof estrogen-induced carcinogenesis. Our current study compared the cumulative body burden ofthese estrogen quinones in serum samples taken from Taiwanese women with breast cancer (n = 152) vshealthy controls (n = 75) by using albumin (Alb) adducts as biomarkers. Results clearly demonstrated thepresence of cysteinyl adducts of E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb in all study population at levelsranging from 61.7–1330 to 66.6–1590 pmol/g, respectively. Correlation coefficient between E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb was 0.610 for controls and 0.767 for breast cancer patients (p < 0.001). Wealso noticed that in premenopausal subjects with body mass index (BMI) less than 27, background levelsof E2-3,4-Q-2-S-Alb was inversely proportional to BMI with about 25% increase in E2-3,4-Q-2-S-Alb per5 kg/m2 decrease in BMI (p < 0.001). In addition, we confirmed that mean levels of E2-3,4-Q-2-S-Alb inbreast cancer patients were∼5-fold greater than in those of controls (p < 0.001). Overall, this evidencesuggests that disparity in estrogen disposition and the subsequent elevation of cumulative body burdenof E2-3,4-Q may play a role in the development of breast cancer