Oxidative Stress, Antioxidants and Breast Cancer Risk

描述(申请人提供)：来自实验室研究的大量证据表明，由雌激素代谢产生的活性氧物种(ROS)在乳腺癌的发生中起着重要作用。这项应用是为了评估全身氧化应激的生物标记物是否与乳腺癌风险有关，在上海的中国女性中大量食用抗氧化剂多酚是否可以降低乳腺癌的风险，特别是在ROS高暴露的人群中。为了实现这些研究目标，我们建议在上海妇女健康研究(RO1CA 70867)的队列中对430例乳腺癌病例和860名单独匹配的对照进行嵌套病例对照研究，这是一项基于人群的队列研究，涵盖了大约75,000名中国女性。除了面对面的访谈，87.5%的队列成员还采集了血液(或口腔细胞)和尿样。在这项拟议的研究中，尿总酚水平将用Folin-Ciocalteu苯酚试剂测定，尿多酚黄酮醇和黄烷醇水平将用液相色谱-二极管阵列电喷雾质谱仪测定，尿2，3-二氢-5，6-二氢-15-F2T-lsoP水平将用气相色谱/负离子化学电离质谱仪测定，血生育酚和类胡萝卜素水平将用高效液相色谱法分析，参与ROS解毒的酶的基因型别将用PCR-RFLP方法测定。这些生物标志物和乳腺癌风险之间的关联将被评估。我们还将进行统计分析，以评估总酚、黄酮醇和黄烷醇与大豆异黄酮类化合物、抗氧化营养素、ROS解毒酶基因型别和氧化应激水平与乳腺癌风险的联合作用或潜在相互作用。鉴于总酚、黄酮醇、黄烷醇和异黄酮类化合物的高摄入量，研究人群将是独一无二的。由于调查问卷数据和样本收集、后续调查以及异黄酮类化合物的分析都得到了现有研究的支持，因此这个项目将非常具有成本效益。此外，如果结果是有希望的，我们还可以将我们的研究扩展到更大的范围。这项研究的发现将对乳腺癌的初级预防具有重要的公共卫生意义。

DESCRIPTION (provided by applicant): Substantial evidence from Iaboratory studies has indicated an important role of reactive oxygen species (ROS), produced by estrogen metabolism, in mammary carcinogenesis. This application is to evaluate whether the biomarker of systemic oxidative stress may be associated with breast cancer risk, whether antioxidant polyphenols, consumed in large quantities among Chinese women in Shanghai, may reduce the risk of breast cancer, particularly among those with a high exposure to ROS. To achieve these research goals, we propose to conduct a nested case-control study of 430 breast cancer cases and 860 individually matched controls within the cohort of the Shanghai Women's Health Study (RO1CA 70867), a population-based cohort study of approximately 75,000 Chinese women. In addition to in-person interviews, blood (or buccal cell) and urine samples were collected from 87.5% cohort members. For this proposed study, urinary level of total phenols will be assayed with Folin-Ciocalteu Phenol Reagent, urinary levels of polyphenol flavonols and flavanols will be determined using liquid chromatography photo-diode array electrospray mass spectrometry, urinary level of 2,3-dinor-5,6-dihydro-15-F2t-lsoP will be quantified by gas chromatography/negative ion chemical ionization mass spectrometry, blood levels of tocopherols and carotenoids will be analyzed using HPLC methods, and genotypes of the enzymes involved in ROS detoxification will be assayed using PCR-RFLP methods. The associations between these biomarkers and breast cancer risk will be evaluated. We also will perform statistical analyses to evaluate the joint effects or potential interactions of total phenols, flavonols and flavanols with soy isoflavonoids, antioxidant nutrients, genotypes of ROS detoxification enzymes and oxidative stress level in relation to breast cancer risk. The study population will be unique given the high intake levels of total phenols, flavonols, flavanols, isoflavonoids. Because questionnaire data and specimen collection, follow-up survey as well as assays for isoflavonoids are supported by the existing study, this project will be very cost-efficient. In addition, we will also be able to expand our study to a larger scale if the results are promising. Findings from this study will have important public health implications in the primary prevention of breast cancer.