Racial and Ethnic Disparities in Survival of Children with Neuroblastoma

We recently demonstrated that African Americans with neuroblastoma have a statistically worse outcome than Caucasian patients. Although multiple factors contribute to health disparities, our studies indicate that genetic factors play a critical role in the overall poor outcome we observed in African American children. Using a unique laboratory, cell-based model, Drs. Dolan and Cox (co-investigator and collaborator, respectively, at the University of Chicago) have identified genetic variants that account for resistance to chemotherapeutic drugs commonly used in the treatment of neuroblastoma. We hypothesize that genetic factors contribute to the high prevalence of clinically aggressive, chemotherapy-resistant neuroblastoma tumors observed in African American children with neuroblastoma. To test this hypothesis, we will evaluate the association between the genetic variants identified in the Dolan laboratory and outcome in a cohort of 2200 neuroblastoma patients. We will also use a novel second generation genome-wide analysis to identify additional genes associated with poor outcome. In collaboration with Dr. Kevin White ( Director of the Institute for Genomics & Systems Biology, University of Chicago), we will use next-generation sequencing to identify rare, inherited genetic factors associated with chemotherapy resistance and poor outcome. Understanding the genetic variables that contribute to ethnic diversity in chemotherapy response in neuroblastoma is critical for the development of more effective, individualized treatment strategies. Further, our studies are likely to have clinical relevance beyond neuroblastoma, as the genetic variants we identify may also prove to be associated with chemotherapy resistance and poor outcome in African American children with other types of cancer.