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Project Number: 3R01CA100374-05S1 Contact PI / Project Leader: ZHENG, WEI
Title: THE NASHVILLE BREAST HEALTH STUDY Awardee Organization: VANDERBILT UNIVERSITY MED CTR
Description
Abstract Text:
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.
NIH Spending Category:
Aging; Breast Cancer; Cancer; Clinical Research; Genetics; Prevention
Project Terms:
Age; Area; Aromatic Polycyclic Hydrocarbons; Biological Assay; Breast; Breast Cancer Prevention; Cancer Etiology; cancer risk; Candidate Disease Gene; Carcinogens; Case-Control Studies; Cells; Chemicals; cooking; cost; CYP1A1 gene; CYP2C9 gene; Data; design; DNA; Drug usage; Enzyme Gene; Enzymes; Estrogen Metabolism; Estrogens; Etiology; Exposure to; Frequencies (time pattern); Future; gene environment interaction; General Population; Genes; Genetic; Genetic Polymorphism; Genotype; Glutathione; GSTT1 gene; Health; Heterocyclic Amines; high risk; High temperature of physical object; Individual; Intake; Interview; lifestyle factors; malignant breast neoplasm; Mammary gland; Mammary Gland Parenchyma; Meat; Metabolism; metropolitan; NAT2 gene; Non-Steroidal Anti-Inflammatory Agents; Oral cavity; Other Genetics; Pharmaceutical Preparations; Phase; population based; Preparation; Prevention strategy; Primary Prevention; Progress Review Group; public health medicine (field); Race; Recruitment Activity; Research; Risk; Sampling; sulfation; System; Telephone; Telephone Interviews; Tennessee; UGT1A1 gene; Woman; Xenobiotic Metabolism



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