The Nashville Breast Health Study

描述(由申请人提供)：这项提案是针对田纳西州纳什维尔的一项基于人群的乳腺癌病例对照研究。其主要假设是1)定期使用非类固醇抗炎药(NSAID)可降低乳腺癌的风险，这种关联可被非类固醇抗炎药代谢酶的基因型改变；2)肉类摄入充足(烧焦)，从而暴露于乳腺癌的致癌物质杂环胺和多环芳烃，可能与乳腺癌的风险增加有关，尤其是在具有某些致癌物质代谢酶基因类型的妇女中；3)经常使用非类固醇抗炎药(NSAID)可改变良好肉类摄入量与乳腺癌风险之间的正相关关系；4)在乳腺癌的病因中，参与雌激素代谢的某些基因可能相互作用。我们建议为这项病例对照研究招募1,500个事件病例和1,500个对照。将通过为这项研究建立的快速病例确定系统来确定乳腺癌病例。对照将从普通人群中随机选择，并按年龄和种族与病例频率匹配。将进行电话访问，以获取相关的暴露信息。将收集口腔脱落细胞样本以提取DNA，用于分析14个候选基因的38个多态，这些基因与非类固醇抗炎药、乳腺癌和雌激素的代谢有关。DNA样本还将被储存，以供未来研究其他遗传因素及其与生活方式因素在乳腺癌风险中的相互作用。 非甾体抗炎药是最常用的药物之一，高温烹饪已被广泛用于肉类准备。关于它们与乳腺癌风险的关系的信息可能对乳腺癌的初级预防具有重要的公共卫生影响。对基因-基因和基因-环境相互作用的研究可以为确定乳腺癌高危个体提供有价值的信息，为设计具有成本效益的乳腺癌预防策略提供有价值的信息。

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.