The Nashville Breast Health Study

纳什维尔乳房健康研究

• 批准号: 7069501
• 负责人: Wei Zheng
• 金额: $ 78.58万
• 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: 2004-06-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7069501
• 关键词: breast neoplasms; cancer risk; carbopolycyclic compound; clinical research; cyclic amine; cytochrome P450; estrogens; female; functional /structural genomics; gene environment interaction; genetic polymorphism; genetic registry /resource /referral center; genetic susceptibility; glucuronosyltransferase; glutathione; heterocyclic polycyclic compound; human genetic material tag; human subject; interview; meat; methyltransferase; nonsteroidal antiinflammatory agent; nutrition related neoplasm /cancer; nutrition related tag

DESCRIPTION (provided by applicant): This proposal is for a population-based case-control study of breast cancer in Nashville, Tennessee. The primary hypotheses are 1) regular use of nonsteroidal anti-inflammatory drugs (NSAID) may reduce the risk of breast cancer, and this association may be modified by the genotypes of NSAID metabolizing enzymes; 2) well-done (charred) meat intake, and thus exposures to the mammary carcinogens heterocyclic amines and polycyclic aromatic hydrocarbons, may be related to an increased risk of breast cancer, particularly among women with certain genotypes of the carcinogen-metabolizing enzymes; 3) the positive association between well-done meat intake and breast cancer risk may be modified by regular NSAID use; 4) certain polymorphic genes involved in estrogen metabolism may interact with each other in the etiology of breast cancer. We propose to recruit 1,500 incident cases and 1,500 controls for this case-control study. Breast cancer cases will be identified through a rapid case-ascertainment system established for the study. Controls will be selected randomly from the general population and frequency-matched to cases by age and race. Telephone interviews will be conducted to obtain relevant exposure information. Exfoliated buccal cell samples will be collected to extract DNA for analyzing 38 polymorphisms in 14 candidate genes that are involved in the metabolism of NSAIDs, mammary carcinogens, and estrogens. DNA samples will also be stored for future studies of additional genetic factors and their interactions with lifestyle factors in the risk of breast cancer. NSAIDs are among the most commonly used medications, and high-temperature cooking has been widely used for meat preparation. Information regarding their associations with breast cancer risk could have important public health implications in the primary prevention of breast cancer. Studies investigating gene-gene and gene-environment interaction could provide valuable information in identifying high-risk individuals for designing cost-effective preventive strategies for breast cancer.

描述（由申请人提供）：该提案针对田纳西州纳什维尔的基于人群的病例对照研究。主要假设是1）定期使用非甾体类抗炎药（NSAID）可能会降低患乳腺癌的风险，并且这种关联可能通过NSAID代谢酶的基因型来改变； 2）肉（烧焦）肉的摄入良好，从而暴露于乳腺癌杂环胺和多环芳族烃，可能与患乳腺癌的风险增加有关，尤其是在具有某些癌变基因代代谢酶基因型的妇女中； 3）良好的肉类摄入量和乳腺癌风险之间的正相关可能会通过常规的NSAID使用来改变； 4）在乳腺癌的病因学中，参与雌激素代谢的某些多态基因可能相互作用。我们建议该病例对照研究招募1,500例事件病例和1,500个对照。乳腺癌病例将通过为研究的快速病例囊肿系统确定。控制措施将从一般人群中随机选择，并按年龄和种族匹配频率与案例匹配。将进行电话采访以获取相关的暴露信息。将收集去角质的颊细胞样品以提取DNA，以分析与NSAID，乳腺癌和雌激素代谢的14个候选基因中的38种多态性。 DNA样品还将存储，以将来研究其他遗传因素及其与乳腺癌风险的生活方式因素的相互作用。 NSAID是最常用的药物之一，高温烹饪已被广泛用于肉类制备。有关其与乳腺癌风险的关联的信息可能会对乳腺癌的主要预防产生重要的公共卫生影响。研究基因基因和基因 - 环境相互作用的研究可以提供有价值的信息，以识别高危个人来设计乳腺癌的具有成本效益的预防策略。