We propose to establish a Molecular Epidemiology Core to support Projects 1,2 and 3. The Core will build upon existing expertise and facilities in the Department of Epidemiology in three areas: collecting and archiving biologic samples from large, population-based epidemiologic studies; high throughput PCR-based genotyping to detect polymorphisms in carcinogen metabolism and DNA repair genes; design and implementation of epidemiologic studies incorporating biomarkers. For Project 1, the Core will provide DNA, red blood cells, and plasma samples from 435 controls from a population-based case-control study of breast cancer in North Carolina. Plasma samples have previously been characterized for PCB levels. The Core will optimize procedures for extraction of DNA and proteins from these samples in order to investigate the relationship between PCB exposure and levels of oxidative stress (AP sites, TG adducts, M1G adducts, oxidized proteins). The Core will conduct assays for metabolism genes and DNA repair genes which modulate endogenous levels of ROS and confer susceptibility to exogenous sources of oxidative DNA damage. For Project 2, the Core will maintain and archive immortalized cell lines from participants in a hospital-based case-control study of breast cancer who have been characterized with a variety of DNA repair and metabolism genes in order to investigate the genetic basis for radiation hypersensitivity. For Project 3, the Core will conduct genotyping assays for metabolism genes which contribute to variability in levels of benzene, benzene metabolites and reactive intermediates in human populations. For Projects 1, 2 and 3, the Core will assist in the implementation of population-based studies incorporating biomarkers, including study design, power calculations, identifying appropriate populations, addressing issues of bias, and obtaining IRB approval.
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