Proteomic Signatures of Cancer

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Environmental substances seem to be involved in the etiology of breast cancers. Several studies have found an association between human cancer and exposure to agricultural pesticides such as the organochlorine (OC) pesticides; therefore, farmworkers may be at higher risk for acute and chronic health effects associated with pesticides. The objective of this project is two-fold, 1) obtain epidemiological data specific to breast cancer incidence rates in areas of high and low pesticide use, and 2) expose normal breast epithelial in culture with organochlorine chemicals to determine the biological effects. This is responsive to the health disparity of Hispanic farmworkers in the Central Valley. For Phase 1, student researchers will calculate age-adjusted breast cancer incidence rates for pesticide use and identify databases from which other variables pertinent to breast cancer epidemiology are useful. Upon promising results, individual breast cancer cases (and healthy "controls") will be approached and recruited for entry into a breast cancer case-control study in which both questionnaire-based information and biological specimens are collected. DNA will be extracted from saliva and genotyped by PCR techniques at Fresno State for several of the common carcinogenmetabolizing genes. For Phase 2, student researchers will test the biological effects of organochlorines on primary normal human mammary epithelial cells derived from Hispanic participants of the NCI/Cooperative Human Tissue Network. Cells maintained under long-term OC treatment will be compared by proteomic expression profiling by 2D-PAGE and LC-MS/MS in year 1 followed by gene expression profiling in year 2. Finally, OC-resistant cells will be screened in conjunction with the BIMR Chemical Genomics Core for reversion of the estrogenic effects. This innovative pilot project takes students through a range of cancer research aspects from identifying at-risk populations to molecular analyses of the problem.