Date on Master's Thesis/Doctoral Dissertation
Pharmacology and Toxicology
Committee Co-Chair (if applicable)
Prostate--Cancer--Genetic aspects; African Americans--Health and hygiene; African Americans--Diseases--Genetic aspects
Background: In the U.S., prostate cancer (PCA) metastasis is associated with a 5-yr survival rate of 29% and disproportionately affects men of African descent. Single nucleotide polymorphisms (SNPs) may serve as genetic markers to identify individuals at high risk of developing PCA. Methods: We examined main and joint effects of 119 inflammatory and immune response-associated SNPs among men of African descent (535 controls, 279 cases) via logistic regression (LR) and entropy-based-multi-factor dimensionality reduction (MDR) modeling. Results: MDR yielded highly synergistic [(TLR10, TLR6 and IRF3), (TLR2, IRAK4), (IL1R2, IL10, IL10RA)] interaction models as the best predictors of PCA risk based upon informative information gain scores (p ≤ 0.003). Interestingly, CCL5 [rs2107538 (AA, GA+AA), rs3817655 (GA, AA)] SNPs were strongly associated with a 43-56% decrease in PCA risk. Conclusion: CCL5 (rs2107538 ,rs3817655) reduces PCA risk by > 50% and may serve as potential targets of PCA treatment among men of African descent.
Jones, Dominique Zilpha, "The impact of inflammatory and immune response-related genetic variants on prostate cancer risk among men of African descent." (2014). Electronic Theses and Dissertations. Paper 1745.