This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study will use a cancer case-control study design to evaluate two hypotheses. The study subjects will include 800 incident breast cancer cases (recruited from the Departments of Surgery and Hematology/Oncology) and 800 controls (frequency-matched by age and race). A self-administered questionnaire will be used to collect data on other known breast cancer risk factors - such as demographic factors, family history of cancer, medication, ionizing radiation exposure, smoking, and ethanol consumption. The first study is to evaluate the role of DNA repair in human breast cancer risk. The working hypothesis is that breast cancer risk is associated with defective/deficient DNA repair. Mitogen-activated peripheral T-lymphocytes will be used for DNA repair functional measurements. Genomic DNA will be used for the determination of genetic variants of DNA repair genes (i.e., XRCC1, XRCC3, XPD, APE, and PARP). The second study is to evaluate the interaction between drug metabolism enzymes, GSTT1/M1 and dietary fat in human breast cancer risk. The working hypothesis is that women with null GSTM1/T1 genotypes cannot effectively detoxify reactive free radicals, which may lead to lipid peroxidation, oxidative DNA damage. Genomic DNA will be used for the GSTT1/M1 genotyping. Plasma samples will be used to measure fatty acid profile and lipid peroxidation levels.
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