title: High levels of oxidative DNA damage in lymphocyte DNA of premenopausal breast cancer patients from Egypt.
abstract: Egypt shows a parallel increase in premenopausal breast cancer and environmental pollution. The purpose of this study is to explore a possible relationship between oxidative DNA damage, urinary estrogen metabolites and breast cancer in Egyptian premenopausal women. We conducted a pilot study of Egyptian breast cancer involving 29 cases and 32 controls and analysed lymphocyte DNA levels of 7,8-dihydro-8-oxo-2'-deoxyguanine (8-oxo-dG), a measure of oxidative DNA damage using high performance liquid chromatography with electro-chemical detection (HPLC-ECD) method. We analysed levels of urinary estrogen metabolites, 2-hydroxyestrone (2-OHE) and 16alpha-hydroxyestrone (16alpha-OHE) by an enzyme immuno assay. We also collected residential, occupational, and reproductive histories of all study subjects. We detected, in all subjects, exceptionally high levels of 8-oxo-dG and thus oxidative DNA damage, the levels (mean 8-oxo-dG/10(5) dG+/-SD) were significantly (P<0.01) higher in breast cancer cases (139.4+/-78.4) than in controls (60.9+/-51.5). Urinary 2-OHE and 16alpha-OHE or their ratio was not significantly different between cases and controls. However, 8-oxo-dG levels were positively correlated (P<0.05) with 2-OHE and 16alpha-OHE from cases while controls showed a negative correlation (P<0.05). Urban residence (Odds Ratio [OR] 3.1; Confidence interval [CI], 1.1-9.3), infertility (OR [9.8]; CI [1.1-89.7]), age (OR [2.6]; CI [1.4-4.6]) and 8-oxo-dG (OR 5.8; CI 1.9-17.5) levels were found to be significant predictors of breast cancer. Our finding of exceptionally high levels of 8-oxo-dG, a common result of oxidative DNA damage, warrant future studies on a larger population of premenopausal women in Egypt with consideration of other susceptibility markers and dietary characteristics.
authors.affiliation: Department of Epidemiology, The University of Michigan School of Public Health, Ann Arbor 48109, USA. asoliman@umich.edu
authors.forename: Amr S
authors.initials: AS
authors.lastname: Soliman
authors.forename: Suryanarayana V
authors.initials: SV
authors.lastname: Vulimiri
authors.forename: Heather E
authors.initials: HE
authors.lastname: Kleiner
authors.forename: Jianjun
authors.initials: J
authors.lastname: Shen
authors.forename: Saad
authors.initials: S
authors.lastname: Eissa
authors.forename: Magda
authors.initials: M
authors.lastname: Morad
authors.forename: Hala
authors.initials: H
authors.lastname: Taha
authors.forename: Farzana
authors.initials: F
authors.lastname: Lukmanji
authors.forename: Donghui
authors.initials: D
authors.lastname: Li
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Johnston
authors.forename: Herng-Hsang
authors.initials: HH
authors.lastname: Lo
authors.forename: Serrine
authors.initials: S
authors.lastname: Lau
authors.forename: John
authors.initials: J
authors.lastname: Digiovanni
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Bondy
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D004534:Egypt; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000506:poisoning; D004967:Estrogens / Q000652:urine; D005260:Female; D006801:Humans; D008214:Lymphocytes; D008875:Middle Aged; D018384:Oxidative Stress; D017697:Premenopause
chemical_list: D004785:Environmental Pollutants; D004967:Estrogens