This career development plan provides a roadmap for the candidate and his mentors to follow in filling gaps in his training that will assist him in achieving independence as a cancer researcher. New knowledge and skills in molecular/genetic epidemiology obtained in the training portion of this award will be applied directly to research examining genetic susceptibility, lifestyle, and cancer risk. Recognition that adipose tissue is both an energy reservoir and a source of proteins with endocrine functions (adipokines), suggests that these proteins, and the genes controlling them, are part of the homeostatic control mechanisms that regulate cell growth. To advance our understanding of the role of energy homeostasis and cancer, epidemiologic studies examining the role of genes involved in energy regulation in humans, as well as the interactions of these exposures with lifestyle factors associated with energy balance are needed. Accordingly, the four aims of this research are as follows. In a case-control study of breast cancer (N=2,500), Aim 1 will examine the effect of polymorphisms in genes involved in energy homeostasis (insulin, IGF-1, leptin, and adiponectin), and Aim 2 will examine gene-environment interactions between these genes and lifestyle factors associated with energy balance (physical activity, energy intake, body size). In a case-control study of adenomatous polyps (N=1,400), Aim 3 will examine the effect of lifestyle factors associated with energy balance (as above), and (Aim 4) will examine the effect of polymorphisms in genes involved in energy homeostasis (as above). Primary research support will come from existing molecular epidemiology studies of the candidate's mentor. Resources from this award will support genotyping of adipokines not originally examined in these studies. This work will extend our understanding of links between energy homeostasis and cancer, as well as interactions between genetic susceptibility, lifestyle factors, and cancer. This work will also serve as the basis for submission of competitive R01 proposals by the candidate in latter years of this award.