This project merges two previous projects into one. The two projects were Environmental and Genetic Factors in Lung Cancer (ES49017) and Magnetic fields, melatonin and breast cancer (ES49018). Both environmental and genetic factors are clearly implicated in cancer etiology. However, susceptibility is clearly important in determining the effect of environmental exposures. This project includes several studies. In lung cancer, there are two major studies. The first is a case-control study of genetic susceptibility to lung cancer in African-Americans and Caucasians in Los Angeles. I conducted this study while a faculty member at the University of Southern California. I have examined a large number of genetic polymorphisms relevant to lung cancer in this study. The study is of modest size by current standards, but is still valuable for examining common polymorphisms. In addition, I am participating in a collaborative study to pool across a number of lung cancer studies to provide sufficient power for studying gene-environment interactions. The second lung cancer study is a collaboration with a prospective cohort study of men in Shanghai, China. This study is based at the University of Southern California. I have been investigating genetic, dietary and environmental factors for lung cancer in this cohort for the past several years. I have done this work using what is called a nested-case control study design. This uses samples from all diagnosed cases of lung cancer and a matched set of controls from the cohort who have not developed cancer. The major strengths of this study are the prospective design and the unique exposures of the Shanghai Cohort. I have published prospective studies of a gene-diet interaction (isothiocyanates and GSTM1 polymorphism) and IGF-1 in relation to lung cancer in the Shanghai Cohort. The genetic studies have used DNA extracted from archival serum samples which presents logistic challenges. This extramurally funded study has recently been renewed for an additional five years of follow-up by NCI. I wrote the portions of the grant dealing with lung cancer. The lung cancer work that was funded includes studying interactions between selenium levels in serum and polymorphisms in selenoproteins and another study of biomarkers of aflatoxin intake in interaction with polymorphisms in DNA repair genes. I will be conducting these two studies using extramural funds. The other component project is a study of magnetic field exposure and breast cancer risk. This is a nested case-control study that I began with extramural funding while a faculty member at USC. From NIEHS, I continued to run this project until the completion of data collection. The main paper from the study was recently accepted for publication. This study was unusual in the prospective design and the inclusion of a predominantly minority populations. The results were negative regarding hazards of residential magnetic field exposure. Given the strong design, these findings should provide reassurance to the public regarding this ubiquitous exposure. In other breast cancer research, I am also a collaborator on the Sister Study having been involved in the initial concept.