Oxidative Stress, Antioxidants and Breast Cancer Risk

描述（申请人提供）：实验室研究的大量证据表明，雌激素代谢产生的活性氧（ROS）在乳腺癌发生中起重要作用。本申请旨在评估全身性氧化应激的生物标志物是否与乳腺癌风险相关，上海中国女性中大量摄入的抗氧化剂多酚是否可以降低乳腺癌风险，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（RO 1CA 70867）的队列中对430例乳腺癌病例和860例个体匹配的对照进行巢式病例对照研究，该研究是一项基于人群的队列研究，约有75，000名中国妇女。除了面对面的访谈，血液（或口腔细胞）和尿液样本收集了87.5%的队列成员。对于这项拟定的研究，将使用Folin-Ciocalteu苯酚试剂测定尿液中总酚的水平，使用液相色谱光电二极管阵列电喷雾质谱法测定尿液中多酚黄酮醇和黄烷醇的水平，使用气相色谱/负离子化学电离质谱法定量尿液中2，3-二去甲-5，6-二氢-15-F2 t-IsoP的水平，使用HPLC方法分析生育酚和类胡萝卜素的血液水平，使用PCR-RFLP方法分析参与ROS解毒的酶的基因型。将评估这些生物标志物与乳腺癌风险之间的关联。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黄酮，抗氧化营养素，ROS解毒酶基因型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。由于总酚、黄酮醇、黄烷醇、甘草酸的高摄入水平，研究人群将是独特的。由于问卷资料及样本收集、跟进调查及样本化验均得到现有研究的支持，故本计划将具成本效益。此外，如果结果有希望，我们也将能够将我们的研究扩大到更大的规模。这项研究的结果将对乳腺癌的一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.