Oxidative Stress, Antioxidants and Breast Cancer Risk

氧化应激、抗氧化剂和乳腺癌风险

• 批准号: 6759765
• 负责人: QI DAI
• 金额: $ 25.89万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6759765
• 关键词: antioxidants; biomarker; blood chemistry; breast neoplasms; cancer prevention; cancer risk; carotenoids; clinical research; dietary constituent; electrospray ionization mass spectrometry; flavonoids; free radical oxygen; gas chromatography mass spectrometry; genotype; high performance liquid chromatography; human subject; interview; liquid chromatography; oxidative stress; phenols; polymerase chain reaction; statistics /biometry; tocopherols; urinalysis; women' s health

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.

描述（由申请人提供）：来自iA型研究的大量证据表明，由雌激素代谢产生的活性氧（ROS）在乳腺癌发生中起着重要作用。该应用是为了评估全身氧化应激的生物标志物是否可能与乳腺癌风险有关，是否在上海中的中国妇女大量消耗的抗氧化剂多酚，是否可能降低患乳腺癌的风险，尤其是在高暴露于乳腺癌的风险中。罗斯。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）中对430例乳腺癌病例和860个单独匹配的对照进行进行嵌套的病例对照研究，这是一项基于人群的同伙研究。女性。除了面对面的访谈外，还从87.5％的队列成员那里收集血液（或颊细胞）和尿液样本。在这项拟议的研究中，将使用叶核酸酚试剂测定总酚的尿液水平5,6-二氢-15-F2T-LSOP将通过气相色谱/负离子化学电离质谱法进行定量，将使用HPLC方法分析生育酚和类胡萝卜素的血液水平，并使用参与ROSOXICAICY的酶的基因型进行分析。使用PCR-RFLP方法。这些生物标志物与乳腺癌风险之间的关联将得到评估。我们还将进行统计分析，以评估总苯酚，黄酮醇和黄酮醇与大豆异类药物，抗氧化剂营养素，玫瑰糖解毒酶的基因型以及氧化应激水平相对于乳腺癌的风险的关节效应或潜在相互作用。鉴于总苯酚，黄酮醇，黄酮醇，异黄酮的摄入量很高，研究人群将是独特的。由于现有研究支持了问卷数据和标本收集，因此对等异类动物的后续调查以及对异黄素的测定，该项目将非常成本效益。此外，如果结果有希望，我们还将能够将研究扩展到更大的规模。这项研究的结果将对乳腺癌的主要预防具有重要的公共卫生影响。