Aims: During the last two years my laboratory has focused its new efforts in susceptibility on DNA repair gene polymorphisms and on the measurement of repair capacity. We believe that molecular epidemiology studies of DNA repair gene polymorphisms and of DNA repair capacity can identify important risks for environmentally-associated cancers. NIEHS provides an ideal environment for molecular epidemiology research on DNA repair. The group of Intramural laboratories working on repair provides a strong basic science foundation of expert colleagues with highly specialized assay systems that facilitates our ability to examine, at the population level, the effects of polymorphisms and repair capacity on mutation and cancer risk. Research on genetic susceptibility and gene-environment interaction may identify variants of genes important to carcinogenesis and the pathways by which environmental agents damage DNA. The study of genetically susceptible subgroups may allow a more precise identification of environmental exposures that cause disease and the risk from such exposure. Finally, if important susceptibility genes are identified, it could lead to public health programs for protecting susceptible populations, and for targeted screening of groups at higher risk of disease. Procedures and techniques: PCR-RFLP, cloning, flow cytometry of GFP, luminometry, DNA transfection Accomplishments: We have demonstrated that polymorphisms in carcinogen metabolism genes and DNA repair genes affect risk of bladder cancer and found evidence for gene-environment and gene-gene interaction. We have demonstrated that polymorphism in DNA repair, vitamin D receptor, and hormone metabolism genes affect risk of prostate cancer. To measure DNA repair capacity we have adapted the host cell reactivation assay to work with two color-shifted co-transfected reporter genes using either luminescence (luciferase, renilla) or fluorescence (GFP, BFP) and have created a novel plasmid construct that provides a measure of homologous recombinational repair of DNA double strand breaks
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