Integrating Innovative Biomarkers of Environmentally Induced Disease for Children in Agricultural CommunitiesEPA Grant Number: R832733
Title: Integrating Innovative Biomarkers of Environmentally Induced Disease for Children in Agricultural Communities
Investigators: Faustman, Elaine
Current Investigators: Faustman, Elaine , Griffith, William C. , Yu, Xiaozhong
Institution: University of Washington - Seattle
Current Institution: University of Washington , University of Washington - Seattle
EPA Project Officer: Callan, Richard
Project Period: October 1, 2005 through September 30, 2008 (Extended to September 30, 2010)
Project Amount: $749,997
RFA: Early Indicators of Environmentally Induced Disease (2004) RFA Text | Recipients Lists
Research Category: Human Health , Health , Biology/Life Sciences , Children's Health , Health Effects
The proposed study is a supplement to our EPA/NIEHS funded Center for Child Environmental Health Risks Research (CHC). We propose to develop an integrative tool for evaluating the importance of knowledge of biomarkers of susceptibility and early response for establishing the exposure-effect-disease relationship in adults and children in agricultural and non-agricultural communities. This study will examine multiple levels of biomarkers including susceptibility, early biological effect, and biomarkers of effect.
As described above, the purpose of this study is to develop an integrative tool for evaluating the importance of knowledge of biomarkers of susceptibility and early response for establishing the exposure-effect-disease relationship in adults and children in agricultural and non-agricultural communities. While there has been more than a decade of research on children in agricultural communities, many unanswered questions remain for both children and adults regarding patterns of exposure and the link between exposure and disease. This proposed study will build on our current study and could significantly advance our understanding of individual susceptibility and early indicators of biological effect. Hypothesis to be tested:
1. Knowing the genotype/phenotype for key genes that metabolize organophosphate (OP) pesticides (biomarkers of susceptibility) will allow for improved prediction of exposure response and will decrease uncertainty factors for predicting at risk individuals in agricultural communities.
2. Knowing polymporphisms of oxidant responsive pathways will allow us to:
- Better evaluate the potential for genomic biomarkers of early response with OP metabolites of exposure.
- Better predict relationship of biomarkers of effect (AChE) to respond in dose-response manner to the OP exposures in adults and children.
- Better predict whether "omic" biomarkers of disease are correlated with OP exposure.
We have the unique opportunity to coordinate this proposed study with an on-going community based participatory research child cohort study in the Yakima Valley (CBPR). This parent study is a part of the EPA/NIEHS funded Center for Child Environmental Health Risks Research (CHC). We will evaluate biomarkers of susceptibility (genotype for pesticide metabolism and oxidative protective pathways) and biomarkers of early biological effect (gene expression responses in oxidative response and cell death) and biomarkers of effect (cholinesterase and clinical disease pathways).
This project will result in five expected products and benefits. First, an integrative tool will be developed for assessing overall risk of developing environmentally induced disease for agricultural populations. This tool will integrate biomarkers of exposure, susceptibility and effect by evaluating key contributors to within and between individual variability in the exposure response pathway. A second result from this matrix will be that it can incorporate knowledge about individual and population based information on genetic susceptibility factors linked with metabolism and response. Third, the tool will utilize a mechanistic based mode of action approach for linking two biomarkers of effect with exposure. The suite of biomarkers to be evaluated in this STAR grant includes innovative "omic" biomarkers for both early response and oxidative stress and apoptosis as well as disease based gene pathways for disease. These biomarkers will be examined in the context of individual exposure over time and within an individual profile of genetic susceptibility for stress response. This project will represent the first time RNA samples have been collected using relatively non-invasive techniques (buccal cell samples) in field conditions. This part of the study will provide important information on biomarker variability and QA/QC information for standardizing such dynamic markers of response for longitudinal cohort studies.