Oxidative stress, obesity and breast cancer risk Free

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Background Overproduction of reactive oxygen species may exhaust the antioxidant capability of human defense systems, leading to oxidative stress, and, in turn, development of breast cancer. There is evidence to suggest that urinary F2-isoprostanes, secondary end products of lipid peroxidation, are more accurate markers of oxidative stress in animal and humans than other available biomarkers. An elevated level of isoprostane has been linked to a number of human diseases and centralized obesity.No prospective study, however, has investigated whether urinary excretion of F2-isoprostanes is related to risk of breast cancer. Methods We have conducted a nested case-control study within the Shanghai Women’s Health Study, a population-based cohort study of 74,942 Chinese women between ages of 40 to 70 years. Urinary F2-isoprostanes were measured by gas chromatography-mass spectrometry for 350 cohort members who developed breast cancer during the follow-up and 681 disease free controls. Results Urinary excretion of F2-isoprostanes was not significantly different between cases and controls. Among overweight controls (body mass index (BMI) over 25), we found that F2-isoprostane level was significantly elevated for those with a higher waist-to-hip ratio (WHR) than those with a lower WHR while this difference was not apparent among controls with a normal BMI. Overall, we did not find that level of F2-isoprostanes was significantly related to breast cancer risk . However, among overweight women, F2-isoprostane level was associated with a non-significantly increased risk of breast cancer; RRs for the second and third tertile levels of F2-isoprostanes were (95%CI) of 1.32 (0.74-2.37) and 1.45 (0.79-2.66) comparing to the lowest tertile(P for trend, 0.24). Among women with a normal BMI, the relative risks (RRs) (95% CI) of developing breast cancer were significantly reduced from 1.0 to 0.80 (0.52-1.24) and 0.58 (0.35-0.93) with increasing tertile of urinary F2-isoprostanes (P for trend, 0.02). The test for multiplicative interaction between BMI and urinary F2-isoprostanes was statistically significant (p for interaction, <0.01). Conclusion Our results suggest that the role of oxidative stress in breast cancer development may depend on adiposity.