Relationship between Urinary 15-F2t-Isoprostane and 8-Oxodeoxyguanosine Levels and Breast Cancer Risk

Abstract

To evaluate the role of oxidative stress in breast cancer, we measured urinary levels of 15-F 2t -isoprostane (15-F 2t -IsoP) and 8-oxodeoxyguanosine (8-oxodG) in 400 cases and 401 controls, participants of the Long Island Breast Cancer Study Project. We also analyzed the effect of different factors that are associated with oxidative stress and might influence 15-F 2t -IsoP and 8-oxodG levels. We observed a statistically significant trend in breast cancer risk with increasing quartiles of 15-F 2t -IsoP levels [odds ratio (OR), 1.25; 95% confidence interval (95% CI), 0.81-1.94; OR, 1.53; 95% CI, 0.99-2.35; OR, 1.88; 95% CI, 1.23-2.88, for the 2nd, 3rd, and 4th quartile relative to the lowest quartile, respectively; P trend = 0.002]. Although it is possible that increased levels may reflect the stress associated with recent treatment, the positive association was also observed when the analyses were restricted to case women for whom chemotherapy and radiation therapy had not yet been initiated at the time of the urine collection. The association with the highest quartile compared with lowest quartile of 15-F 2t -IsoP was similar across strata of age, physical activity, fruit and vegetable intake, alcohol intake, cigarette smoking, body mass index, and menopausal status. We did not observe any association of breast cancer risk with 8-oxodG levels, but when cases with radiation treatment were removed from the analysis, a significant inverse trend (P = 0.04) was observed. Among controls, levels of 15-F 2t -IsoP were higher among current cigarette smokers but did not differ by the amount of physical activity, fruit and vegetable intake, alcohol intake, body mass index, and menopausal status. Among controls, levels of 8-oxodG were higher among postmenopausal women and current and former cigarette smokers but did not differ by the other factors. In summary, our results suggest that urinary markers of lipid peroxidation and oxidative DNA damage may be associated with breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(4):639 -44)

The Role of Biomarkers of Oxidative Stress in Breast Cancer Risk and Prognosis: A Systematic Review of the Epidemiologic Literature

“…In a population-based case-control study of 400 cases and 401 controls from the Long Island Breast Cancer Study Project, a positive association was reported for urinary 15-F 2t -IsoP measured via immunoassay and risk of breast cancer, but not urinary 8-oxodG measured by competitive enzyme-linked immunosorbent assay (ELISA). 40 All samples for the cases were collected within on average 3 months after diagnosis of breast cancer, with most before the initiation of chemotherapy. The positive association between 15-F 2t -IsoP and increased risk of breast cancer was found among both pre-and postmenopausal women.…”

Administration of omega-3 fatty acids and Raloxifene to women at high risk of breast cancer: interim feasibility and biomarkers analysis from a clinical trial

“…Lovaza administration, on the other hand, did not influence IGF-I levels as also observed by Yee et al 15 Whether increased oxidative stress, inflammation and preferential estrogen metabolism toward the pro-carcinogenic 16-a-hydroxylated metabolite have a role in breast cancer development remains uncertain at this time in view of conflicting reports in the literature. [23][24][25] With regard to the role of oxidative stress and inflammation, a major issue is the appropriate selection of the most relevant biomarkers. Therefore, the lack of an effect of our interventions on select biomarkers of inflammation and oxidative stress does not necessarily rule out a role of cellular stress and inflammation on breast cancer development or an antitumor action of our combined treatments.…”

Oral administration of Pyrrolidine Dithiocarbamate (PDTC) inhibits VEGF expression, tumor angiogenesis, and growth of breast cancer in female mice

“…Recent clinical and experimental findings suggest that oxidative stress is associated with the progression of breast cancer. [3][4][5][6] Thus, it is very important to identify the biological effects of the antioxidant compounds, such as PDTC, to antagonize the deleterious action of ROS related to carcinogenesis and cancer progression. A recent study showed that intravenous administration of PDTC reduced tumor growth in nude mice using MCF-7 sphere cells as model of breast cancan stem-like cells.…”

“…1,2 Recent clinical and experimental findings suggest that oxidative stress is associated with the progression of breast cancer. [3][4][5][6] Oxidative damage of DNA has been implicated in the initiation of mammary tumors. [7][8][9] Aside from the role of oxidants in the induction of mutation, oxidative stress also mediates cell signaling pathways involved with increasing mutation rate, activating growth-promoting signaling pathways, stimulating tumor angiogenesis, and accelerating tumor progression.…”