Imbalances in the disposition of estrogen and naphthalene in breast cancer patients: a potential biomarker of breast cancer risk.

Abstract

Elevation of naphthoquinones and estrogen quinones, which are reactive metabolites of naphthalene and estrogen, is thought to be an important indicator of naphthalene- and estrogen-induced carcinogenesis. We compared background levels of naphthalene and estrogen quinone-derived adducts in serum albumin (Alb) from 143 women with breast cancer and 119 healthy controls. Cysteinyl adducts of naphthoquinones, including 1,2-naphthoquinone (1,2-NPQ) and 1,4-naphthoquinone (1,4-NPQ), and estrogen quinones, including estrogen-2,3-quinones (E2-2,3-Q) and estrogen-3,4-quinones (E2-3,4-Q), were characterized after adduct cleavage. Levels of estrogen quinones and naphthoquinones were positively correlated in healthy controls, but not in breast cancer patients (p < 0.05). Compared with controls, levels of 1,2-NPQ and E2-3,4-Q were elevated by two- to ten-fold in cancer patients (p < 0.001). To explore the correlation between estrogen- and naphthalene-derived quinone adducts and disease status, we performed linear discriminant analysis of the ratio of 1,2-NPQ-Alb to (1,2-NPQ-Alb plus 1,4-NPQ-Alb) versus the ratio of E2-3,4-Q-2-S-Alb to (E2-2,3-Q-4-S-Alb plus E2-3,4-Q-2-S-Alb) in patients and controls. These two groups were separable using albumin adducts of estrogen quinones and naphthoquinones, with 99.6% overall correct classification rate (overall accuracy). The findings of this study suggest that differences in the disposition of estrogen and naphthalene, and the subsequent elevation of cumulative E2-3,4-Q and 1,2-NPQ may serve as biomarkers of breast cancer risk.

• Authors: Dar-Ren Chen, Wei-Chung Hsieh, Yi-Lun Liao, Kuo-Juei Lin, Yu-Fen Wang, Po-Hsiung Lin
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 11773 (07 16 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32678225 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Estrogens
• Naphthalenes

Topics

• Adult
• Aged
• Biomarkers, Tumor
• Breast Neoplasms (blood, diagnosis, etiology)
• Case-Control Studies
• Disease Susceptibility
• Estrogens (blood)
• Female
• Gas Chromatography-Mass Spectrometry
• Humans
• Middle Aged
• Naphthalenes (blood)
• Prognosis
• Risk
• Young Adult