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.
Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan; Department of Environmental Engineering, National Chung Hsing University, Taichung, Taiwan.
Che
C
Lin
Department of Internal Medicine, Da-Chien General Hospital, Miaoli, Taiwan.
Wei-Chung
WC
Hsieh
Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan.
Dar-Ren
DR
Chen
Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan.
Shou-Jen
SJ
Kuo
Department of Internal Medicine, Da-Chien General Hospital, Miaoli, Taiwan.
Wen-Fa
WF
Yu
College of Oral Medicine, Chung Shan Medical University, Taiwan.
Suh-Woan
SW
Hu
Department of Environmental Engineering, National Chung Hsing University, Taichung, Taiwan.
Hung-Jie
HJ
Sue
Department of Environmental Engineering, National Chung Hsing University, Taichung, Taiwan.
Mao-Hui
MH
Ko
Department of Environmental Engineering, National Chung Hsing University, Taichung, Taiwan.
Chang-Hsin
CH
Juan
Department of Environmental Engineering, National Chung Hsing University, Taichung, Taiwan.
Kuo-Suan
KS
Chung
Department of Environmental Engineering, National Chung Hsing University, Taichung, Taiwan. Electronic address: pohsiunglin@yahoo.com.
Po-Hsiung
PH
Lin
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D008875:Middle Aged; D015203:Reproducibility of Results; D013624:Taiwan; D055815:Young Adult
D014408:Biomarkers, Tumor; D006454:Hemoglobins; C500988:estradiol-3,4-quinone; C049872:estradiol-2,3-O-quinone; D004958:Estradiol
Biomarkers; Protein adducts; Quinones; Tissue dose