This Specialized Cooperative Center for Nutrient-Gene Interaction (CNGI) will focus on the identification of genetic pathways that may distinguish cancer cell development from normal cells, and the extent to which dietary polyphenols with documented chemopreventive activity modulate these pathways. The effect of polyphenols on mammary epithelial cells, believed to be the targets of initiating events in carcinogenesis, will be studied by an interdisciplinary team of investigators and consultants from the University of Alabama at Birmingham, the Northern California Cancer Center and the University of Missouri-Rolla. The team will use a combination of genomics, epidemiology, DNA microarray, and proteomic approaches to understand the events that take place during puberty, a critical period from a chemoprevention standpoint, as the cells of the breast come under the control of increasing amounts of estrogenic and other steroid hormones. The general hypothesis is that gene and protein expressions are modulated (or altered) by polyphenols to program a life-long reduction in breast cancer as well as prostate cancer risks. The hypothesis will be examined using a cell culture approach (project 1) and animal chemoprevention studies (project 2). The effect of polyphenols on gene and protein expression in the prostate of mice will address a parallel issue occurring during puberty in males. In project 3, a cohort epidemiological study in Asian girls (10-13 years old) who are soy- and non-soy consumers will determine whether soy consumption alters the timing of menarche, a risk factor for breast cancer. The relationship between the polymorphisms of genes encoding the synthesis and metabolism and mode of actions of steroid hormones and the onset of menarche will also be examined. For these DNA microarray and proteomics approaches, there is a need for a higher level of statistics than is currently available - project 4 will focus on the development and evaluation of new statistical procedures for analysis of the types of data produced by the high dimensional nature of each of the projects 1-3. The Center's research activities will be supported by three cores - a Genomics Core (Core A), responsible for gene sequencing and SNP analyses of specific variants (project 3) and microarray analysis (projects 1-2), a Proteomics Core (Core B), responsible for protein analyses from projects 1-3, and a Biostatistics/Bioinformatics Core (Core C) that will provide support to all projects and Cores. In addition to the main projects, the Center will organize a competitive Pilot Project/Developmental program for the evaluation of new ideas and methods pertinent to the overall development of the Center.
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