The Nashville Breast Health Study

描述（由申请人提供）：本提案是在田纳西州纳什维尔进行的一项基于人群的乳腺癌病例对照研究。主要假设是：1)定期使用非甾体类抗炎药（NSAID）可降低乳腺癌风险，这种关联可能受NSAID代谢酶基因型的影响；2)熟肉的摄入，从而暴露于乳腺癌致癌物杂环胺和多环芳烃中，可能与乳腺癌风险增加有关，特别是在具有某些致癌物质代谢酶基因型的妇女中；3)定期使用非甾体抗炎药可能会改变熟肉摄入量与乳腺癌风险之间的正相关关系；4)参与雌激素代谢的某些多态性基因可能在乳腺癌的病因学中相互作用。我们建议在本病例对照研究中招募1500例事件病例和1500例对照。乳腺癌病例将通过为该研究建立的快速病例确定系统来确定。对照将从一般人群中随机选择，并根据年龄和种族与病例进行频率匹配。将进行电话访谈，以获取相关暴露信息。将收集脱落的口腔细胞样本，提取DNA，分析涉及非甾体抗炎药、乳腺癌和雌激素代谢的14个候选基因的38个多态性。DNA样本也将被储存起来，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。

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.