Nashville Breast Health Study

Awarding Agency:  Vanderbilt University – sub award
Award No:  5 R01 CA100374
Principal Investigator: Alecia Malin Fair, DrPH
Co-Principal Investigator:  Regina Offodile, M.D.

Grant Summary:  This proposal is for a population-based case-control study of breast cancer in the Nashville Metropolitan area. 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 mammary carcinogens heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (yARs), may be related to an increased risk of breast cancer, particularly among women with certain genotypes of the enzymes inv9lved in HCA and PAR metabolism; 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. To evaluate the above hypotheses, we propose to accomplish the following specific aims in the study:

1)   To recruit 1500 incident breast cancer cases and 1500 frequency-matched controls in Nashville, TN;
2)   To phone-interview subjects for information on NSAID use, well-done meat intake, and other lifestyle factors;
3)   To collect exfoliated buccal cell samples through mouth rinsing and extract DNA from these samples;
4)   To perform genotyping assays for polymorphisms in genes encoding the following phase I enzymes (CYP 1 Al, CYPIB1, CYP2C9, EH) and phase II enzymes involved in glucuronidation (UGT1AI, UGTIA6), sulfation (SULTIAI), or transfer of acetyl (NAT1, NAT2), methyl (COMT), or glutathione (GSTAI, GSTMI, GSTP1, GSTT1) groups. The genes for these enzymes are expressed in the target breast tissue, and these genes were selected to provide a comprehensive genommic analysis of mammary metabolism of xenobiotic (NSAID, HCA, PAR) and endobiotic (estrogen) chemicals. The polymorphisms of these genes are summarize4 in Table B 1 and discussed in detail in Sections BI to B7.
5)   To perform statistical, analysis to evaluate the hypotheses described above;
6)   To store DNA samples for future study of other genetic factors.

This proposed study will investigate several important etiologic hypotheses for breast cancer that have not been adequately evaluated in previous studies. In particular, NSAIDs are among the most commonly used medications, and high-temperature cooking has been widely used for meat preparation, particularly in southern states, such as Tennessee. Information regarding their associations with breast cancer risk could be valuable in the prevention of breast cancer. The research to investigate gene-gene and gene-environment interaction is one of the two priorities identified by the NCI Breast Cancer Progress Review Group in the area of etiology Such studies hold great promise both for providing essential data needed to design rational preventive strategies for high-risk populations and furthering our fundamental understanding of breast cancer etiology.