Hemoglobin adducts as biomarkers of estrogen homeostasis: elevation of estrogenquinones as a risk factor for developing breast cancer in Taiwanese women.

The aim of this study was to establish a methodology to analyze estrogen quinone-derived adducts, including 17β-estradiol-2,3-quinone (E2-2,3-Q) and 17β-estradiol-3,4-quinone (E2-3,4-Q), in human hemoglobin (Hb). The methodology was then used to measure the levels of these adducts in Hb derived from female breast cancer patients (n=143) as well as controls (n=147) in Taiwan. Our result confirmed that both E2-2,3-Q- and E2-3,4-Q-derived adducts, including E2-2,3-Q-4-S-Hb and E2-3,4-Q-2-S-Hb, were detected in all breast cancer patients with median levels at 434 (215-1472) and 913 (559-2384) (pmol/g), respectively. Levels of E2-2,3-Q-4-S-Hb correlated significantly with those of E2-3,4-Q-2-S-Hb (r=0.622-0.628, p<0.001). By contrast, median levels of these same estrogen quinone-derived adducts in healthy controls were 71.8 (35.7-292) and 139 (69.1-453) (pmol/g). This translated to ~6-fold increase in mean values of E2-2,3-Q-4-S-Hb and E2-3,4-Q-2-S-Hb in breast cancer patients compared to those in the controls (p<0.001). Our findings add further support to the theme that cumulative body burden of estrogen quinones is an important indicator of breast cancer risk. We hypothesize that combination of genetic events and environmental factors may modulate estrogen homeostasis and enhance the production of estrogen quinones which lead to subsequent generation of pro-mutagenic DNA lesions in breast cancer patients.