ASPO Abstracts
RNA Splicing Regulatory SNPs Associated With Prostate Cancer Racial Disparities
Category: Cancer Health Disparities, Molecular Epidemiology & Environment
Conference Year: 2018
Abstract Body:
Racial differences in prostate cancer (PCa) aggressiveness and mortality are significant. These disparities persist after adjustment for social determinants of health, suggesting genetic factors make an important contribution to such disparities. Dysregulation of RNA splicing can drive cancer. We identified differences in expression of RNA splice variants between African American (AA) and white PCa, and the functional significance of AA-enriched variants to PCa aggressiveness. A subset of variants were also present in the patient’s adjacent normal prostate, suggesting germline origination of differential RNA splicing as a novel mechanism of race-related PCa aggressiveness. Single nucleotide polymorphisms (SNPs) in splicing regulatory regions of these genes have the potential to drive the RNA splicing. Using genome-wide association study data, we evaluated associations between SNPs in race-related differentially spliced genes and related oncogenic signaling networks and PCa risk, aggressiveness and survival, and performed in silico bioinformatics to predict SNP function. We identified SNPs in stemness-related genes that were associated with PCa risk, with SNPs showing heterogeneity in susceptibility between African descendants and non-Hispanic whites and SNPs only in African descendants. A number of these SNPs were predicted to regulate RNA splicing. We also identified SNPs in the genes that were associated with PCa survival in non- Hispanic whites and predicted to regulate RNA splicing. Finally, we identified associations between SNPs in race- related differentially spliced genes functioning in sustaining proliferation, deregulating cellular energetics, resisting cell death, inducing angiogenesis, activating invasion and metastasis and tumor-promoting inflammation that associate with PCa risk and aggressiveness in non-Hispanic whites and African descendants, and survival in non- Hispanic whites. All of these SNPs were predicted to regulate RNA splicing. This work elucidates predicted RNA splicing regulatory SNPs that associate with PCa risk, aggressiveness and/or survival. Our findings will contribute to understanding aggressive PCa biology and PCa racial disparities and to precision medicine by informing individualized risk prediction models for PCa aggressivene
Keywords: RNA Splicing Cancer Disparities Splice-regulatory SNPs Prostate Cancer