Rossner Pavel, Gammon Marilie D, Terry Mary Beth, Agrawal Meenakshi, Zhang Fang Fang, Teitelbaum Susan L, Eng Sybil M, Gaudet Mia M, Neugut Alfred I, Santella Regina M
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):639-44. doi: 10.1158/1055-9965.EPI-05-0554.
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.
为评估氧化应激在乳腺癌中的作用，我们测量了长岛乳腺癌研究项目中400例病例和401例对照者尿液中15-F(2t)-异前列腺素（15-F(2t)-IsoP）和8-氧代脱氧鸟苷（8-oxodG）的水平。我们还分析了与氧化应激相关且可能影响15-F(2t)-IsoP和8-oxodG水平的不同因素的作用。我们观察到，随着15-F(2t)-IsoP水平四分位数的增加，乳腺癌风险呈统计学显著趋势[比值比（OR），1.25；95%置信区间（95%CI），0.81 - 1.94；OR，1.53；95%CI，0.99 - 2.35；OR，1.88；95%CI，1.23 - 2.88，分别为第二、第三和第四四分位数相对于最低四分位数；P（趋势）=0.002]。尽管水平升高可能反映了与近期治疗相关的应激，但当分析仅限于在尿液收集时尚未开始化疗和放疗的病例女性时，也观察到了正相关。与15-F(2t)-IsoP最低四分位数相比，最高四分位数与乳腺癌的关联在年龄、身体活动、水果和蔬菜摄入量、酒精摄入量、吸烟、体重指数和绝经状态各分层中相似。我们未观察到乳腺癌风险与8-oxodG水平有任何关联，但当从分析中排除接受放疗的病例时，观察到显著的负向趋势（P = 0.04）。在对照者中，当前吸烟者的15-F(2t)-IsoP水平较高，但在身体活动量、水果和蔬菜摄入量、酒精摄入量、体重指数和绝经状态方面无差异。在对照者中，绝经后女性以及当前和既往吸烟者的8-oxodG水平较高，但在其他因素方面无差异。总之，我们的结果表明，脂质过氧化和氧化性DNA损伤的尿液标志物可能与乳腺癌风险相关。
