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 16α-hydroxyestrone (16α-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/105 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 16α-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 16α-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.