The substantial systemic effects of DR suggest to the applicant that there is a subset of serum metabolites that differ between AL and DR rats and reflect the physiological benefits of reduced caloric intake. The central hypothesis of the proposed studies is that these metabolites are markers of physiological status and that they will be associated with the relative risk o developing a disease against which DR protects, even in different species. The applicants proposes to test this hypothesis and apply it to the specific case of breast cancer.
Specific aims are: 1) to define serotypes that reflect differences in caloric intake and 2) to test the hypothesis that patterns characteristic of AL and DR serum phenotypes predict relative risk of breast cancer in humans. Application of pattern recognition techniques to metabolic profile data obtained from food restriction of variable duration in rats will be done to identify metabolite profiles that are independent of recent food intake, but associated with long term AL or DR regimens in both male and femal rats of various ages (6, 12, 18, 24, 30 months). Both individual serum metabolites and the metabolic profiles will then be tested for their ability t predict future development of breast cancer using banked human blood samples. Successful completion of the aims of this proposal will identify metabolite profiles of long and short term AL or DR feeding in rats, test for the presenc and reproducibility of these patterns in humans and test the hypothesis that profiles that reflect long term DR are associated with reduced relative risk for future development of breast cancer in humans.
