BACKGROUND & AIMS:
:Reactive oxygen species (ROS), normally generated through biologic processes, may damage DNA, lipids, and proteins. ROS are balanced through enzymatic mechanisms and exogenous antioxidants; imbalance results in oxidative stress. Limited data suggest an association between oxidative stress and breast cancer. We evaluated pre-diagnostic plasma fluorescent oxidation products (FlOP), a global biomarker of oxidative stress, and breast cancer risk in a nested case-control study in the Nurses' Health Study. Participants provided two blood samples (1989-1990 and 2000-2002) (N = 18,743). 377 women developed breast cancer between the second collection and June 1, 2006. Cases were matched to 377 controls. Relative fluorescent intensity at three different excitation/emission wavelengths (FlOP_360, FlOP_320, FlOP_400) were quantified in both samples, providing distant (≥10 years before diagnosis) and proximate (≤6 years before diagnosis) measures of oxidative stress. We observed no association between FlOP and breast cancer risk in proximate or distant samples (e.g., proximate extreme quartiles: FlOP_360, RR 0.8, 95 % CI 0.5-1.3, p trend = 0.49; FlOP_320, RR 1.1, 95 % CI 0.7-1.7, p trend = 0.53; FlOP_400, RR 1.3, 95 % CI 0.8-2.0, p trend = 0.80). In general no association was observed when cross-classifying or averaging proximate and distant exposure (e.g., extreme quartile of averages: FlOP_360, OR 0.9, 95 % CI 0.6-1.4, p trend = 0.82; FlOP_400, OR 0.9, 95 % CI 0.6-1.4, p trend = 0.55), with the exception of a significant trend for average FlOP_320 (extreme quartiles, OR 1.6, 95 % CI 1.0-2.4, p trend = 0.02). We did not observe important associations between FlOP and breast cancer risk in this large prospective study, though our data suggest women with consistently high FlOP_320 may be at increased risk.
背景与目标:
: 通常通过生物过程产生的活性氧 (ROS) 可能会损害DNA,脂质和蛋白质。ROS通过酶促机制和外源抗氧化剂进行平衡; 不平衡导致氧化应激。有限的数据表明氧化应激与乳腺癌之间存在关联。我们在护士健康研究的巢式病例对照研究中评估了诊断前血浆荧光氧化产物 (FlOP),氧化应激的全球生物标志物和乳腺癌风险。参与者提供了两个血液样本 (1989-1990和2000-2002) (N = 18,743)。在第二次收集和2006年6月1日之间,有377名妇女患了乳腺癌。病例与377对照相匹配。在两个样品中定量了三种不同激发/发射波长 (FlOP_360,FlOP_320,FlOP_400) 下的相对荧光强度,提供了远处 (诊断前 ≥ 10年) 和近处 (诊断前 ≤ 6年) 的氧化应激测量。我们在邻近或远处的样本中没有观察到翻牌与乳腺癌风险之间的关联 (例如,邻近的极端四分位数: FlOP_360,RR 0.8,95% CI 0.5-1.3,p趋势 = 0.49; FlOP_320,RR 1.1,95% CI 0.7-1.7,p趋势 = 0.53; FlOP_400,RR 1.3,95% CI 0.8-2.0,p趋势 = 0.80)。通常,当对邻近和远处暴露进行交叉分类或平均时,没有观察到关联 (例如,平均值的极端四分位数: FlOP_360或0.9,95% CI 0.6-1.4,p趋势 = 0.82; FlOP_400或0.9,95% CI 0.6-1.4,p趋势 = 0.55),除了平均FlOP_320的显著趋势 (极端四分位数,或1.6,95% CI 1.0-2.4,p趋势 = 0.02)。在这项大型前瞻性研究中,我们没有观察到FlOP与乳腺癌风险之间的重要关联,尽管我们的数据表明,FlOP_320持续高的女性风险可能会增加。