Nutrition and Cancer Prevention
Diet-gene interactions relevant to cancer prevention, particularly the molecular and hormonal mechanisms underlying energy balance-cancer associations.
1. Mechanism-Based Nutrition and Cancer Prevention Studies in Genetically Engineered Mice. Our work has focused on developing and using genetically altered mouse models to identify preventive, particularly nutritional, approaches to offset the increased cancer risk due to a genetic lesion such as loss of p53 or APC tumor suppressor activity or overexpression of growth signaling molecules including Wnt-1 and insulin-like growth factor-1 (IGF-1).
2. Mechanisms Underlying the Energy Balance and Carcinogenesis Relationship: The Roles of IGF-1, Leptin and Inflammatory Pathways. Obesity is an important risk factor for several human cancers, and the prevention of obesity via diet changes, physical activity, and pharmacologic interventions in animal models suppresses tumor development and extends lifespan. We are currently testing the hypothesis that the anticancer and antiaging effects of these interventions are mediated by reduced levels of IGF-1 leptin, and inflammatory factors. Using oligonucleotide microarrays and other molecular approaches, we are evaluating the molecular changes in response to dietary energy restriction with and without IGF-1 and/or leptin replacement. In addition, we are comparing other energy balance-modulating interventions, such as exercise, fasting, alcohol, phytochemicals, and a diet-induced obesity regimen to determine the key pathways linking energy balance and carcinogenesis.
3. Translational Nutrition and Chemoprevention Studies. We are collaborating with epidemiologists and clinical investigators to evaluate the effects of breast cancer chemopreventive agents including tamoxifen, raloxifene and aromatase inhibitors in combination with dietary or physical activity interventions in breast cancer clinical trials, and with several colleagues on preclinical studies of combinations of chemopreventive agents, dietary interventions and anticancer vaccines.