Background: This proposal will provide training to conduct research to understand racial disparities in tobacco-associated morbidity among children. Exposure to environmental smoke tobacco (ETS) remains a major public health hazard for children. Although African Americans are reportedly exposed to less ETS, they have disproportionately higher rates of asthma, low-birth weight, sudden infant death syndrome and higher levels of pre-cancerous compounds known as DMA adducts. Few studies have attempted to explain racial differences in DNA adducts by accounting for both environmental and genetic factors in children. Objectives: The objectives of this proposal are: 1) to examine the longitudinal relationship between ETS exposure and white blood cell (WBC) DNA adducts;2) to test for racial differences in the level of WBC DNA adducts;3) to determine whether polymorphisms in key genes explain the relationship between African American race and levels of WBC DNA adducts. Methods: This proposed project will use prospectively collected data and biologic samples from an NIH-funded asthma intervention trial. Using objective measures of ETS exposure and a 32P-postlabeling technique to measure levels of WBC DNA adducts, we will delineate the longitudinal relationship between children's ETS exposure and the formation of WBC DNA adducts. To understand how genetic polymorphisms influence racial differences in DNA adducts, we will explore whether polymorphisms in 4 candidate genes (GSTM1, GSTT1, GSTP1, and NAT2) modify the relationship between African American race and WBC DNA adducts. Training: To achieve the goals outlined in this proposal, I plan to pursue additional training in molecular epidemiology, cancer prevention, and advanced research methods. This training - coupled with mentorship from Drs. Bruce Lanphear and Robert Kahn and expertise from other advisors with extensive topical expertise - will prepare me to conduct inter-disciplinary research on the complex relationship of genetic predisposition and environmental exposures on children's health. Implications: The long-term goals of this training award will include a series of independently funded efforts to explore the effects of other polymorphisms on DNA adducts, and to test interventions that reduce DNA adduct levels in tobacco-exposed children.
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