The Smoking and Embryonal Tumor (SETs) study is a population-based study of retinoblastoma among California children. California has unique resources: 1) a large population allowing for sufficient cases of disease to study rare cancers; 2) stored neonatal blood spots that the state makes available for research; and 3) a Cancer Registry operating since 1988. We have almost a decade of experience studying the epidemiology of retinoblastoma in California and worldwide and studying environmental and dietary exposures. Using funding from California?s Tobacco-Related Disease Research Program, we previously conducted broad- scale metabolomics of biosamples to examine biomarkers of tobacco use in 498 cases and 895 controls. We propose to employ these data in a new and innovative manner combining our expertise in retinoblastoma epidemiology with the resources in Dr. Jones? laboratory to identify metabolomics exposure markers and potential disease biomarkers for pediatric retinoblastoma. Metabolomics data analyses will be conducted in a targeted as well as untargeted manner to identify and quantify a number of prenatal exposures and their metabolites in neonatal blood spots. This novel approach will be used to identify exposure and disease ?signatures? from metabolites in human metabolic pathways and environmental exposures. This will help us test existing and generate new hypotheses about maternal exposures (e.g. diet, environmental exposures) and metabolic states that affect cancer development in the offspring. We expect this application to encourage environmental policies and provide strategies for population-based prevention of cancer.
Here we propose to build upon a unique resource ? a population-based case-control study of childhood cancer among California children for which our group has conducted broad-scale metabolomics? to identify biomarkers of retinoblastoma risk in early life. We will conduct a metabolome-wide association study (MWAS) to look for biomarkers of retinoblastoma as well as to conduct quasi-targeted analyses of metabolomics data to test hypotheses of risk factors. Our goal is to evaluate the 'internal environmental exposome' for these newborns and examine its relation to retinoblastoma risk.
