Diessner, Brandon2020-10-262020-10-262020-08https://hdl.handle.net/11299/216891University of Minnesota Ph.D. dissertation. August 2020. Major: Epidemiology. Advisor: Logan Spector. 1 computer file (PDF); vii, 110 pages.The risk factors for the development or progression of sarcomas remain mostly obscure. This is largely due to the extreme rarity of the disease, oftentimes constraining investigators to evaluate histologically distinct sarcoma subtypes as a single group or else risk analyses of insufficiently low statistical power. In this dissertation, we aimed to evaluate the genetic and non-genetic risk factors for the development or progression of individually rare subtypes of sarcoma. The first project utilized the SEER Census Tract-level Socioeconomic Database to assess the associations of census tract-level socioeconomic status (CT-SES) or race/ethnicity on the incidence rates or odds of metastasis at diagnosis for sarcoma subtypes diagnosed across the age span. Overall, we found race/ethnicity to be more often associated with sarcoma incidence than CT-SES, particularly in younger age groups. Additionally, in adults, we found SES-related factors increased the odds of metastasis at diagnosis for several soft tissue sarcomas, but not bone sarcomas. In Project 2, we aimed to describe the contribution of common genetic variation to osteosarcoma (OS) development by leveraging a newly created dataset of open chromatin regions (OCR) of osteoblasts. We found an enrichment of OS-associated loci in these regions, indicating that several common variants contribute a weak or moderate effect on osteosarcoma development by altering regulatory mechanisms that localize to an osteoblast’s OCR. Lastly, we sought to determine the associations of risk alleles discovered by GWAS in Europeans and genetic ancestry on Ewing sarcoma (ES) risk in Latinos. We found the effect of these alleles generalize to Latinos. Additionally, we report a residual inverse association between African genomic ancestry and ES risk. These data indicate that other ancestry-specific genetic variants may influence ES susceptibility and explain the observed racial disparities. Overall, our findings add to the scientific knowledge of an exceedingly understudied group of cancers.enancestrygeneticssarcomaThesis or Dissertation