Diana Diaz

Date of Award

Summer 2019

Document Type

Open Access Thesis

Department

Epidemiology and Biostatistics

First Advisor

Susan Steck

Abstract

Prostate cancer incidence and mortality have been decreasing in recent years, but it remains the most commonly diagnosed cancer among men. Racial disparities exist in prostate cancer with African Americans (AAs) having notably higher rates of incidence and mortality, lower survival rates, and are more likely to be diagnosed with a highergrade cancer compared to European Americans (EAs). Genome-wide association studies have revealed several single nucleotide polymorphisms (SNPs) within the vitamin Drelated GC gene that may be associated with prostate cancer aggressiveness. In addition to SNPs, previous research has suggested that low levels of 25-hydroxyvitamin D (25(OH)D) may be related to prostate cancer risk and aggressiveness, though studies are inconsistent. Low levels of 25(OH)D are more common among AAs than other racial/ethnic groups, thus vitamin D and related genes may play a role in prostate cancer racial disparities. The current study utilized data from the North Carolina-Louisiana Prostate Cancer Project (PCaP) to assess the relationship between 28 GC SNPs, the combined genotypes for rs7041 and rs4588, and a polygenic risk score with low levels of 25(OH)D and aggressive prostate cancer in AAs (n=524) and EAs (n=657). None of the combined genotype categories were significantly associated with aggressive prostate cancer among AAs, and only one significantly decreased risk among EAs (Gc1s-1s, OR: 0.38, 95% CI: 0.17, 0.85). Significant associations with aggressive prostate cancer were observed in the additive and dominant genetic models, but not the recessive model. Two SNPs in AAs (rs222054 and rs16847028) and one SNP in EAs (rs6817912) significantly decreased the risk of high aggressive prostate cancer. Four SNPs among AAs (rs4588, rs2282679, rs3755967 and rs17467825) and eight SNPs among EAs (rs4588, rs7041, rs222040, rs705119, rs705120, rs2282679, rs3755967 and rs17467825) significantly increased the risk of having low levels of 25(OH)D. A polygenic risk score of two SNPs (rs4588-CC and rs222054-CC) reflecting higher levels of 25(OH)D significantly decreased the risk of high aggressive prostate cancer among AAs. There was no evidence of interaction between the polygenic risk score and 25(OH)D on the association with aggressive prostate cancer. This study identified two SNPs GCrs4588 and GCrs222054 that appear to affect levels of vitamin D and prostate cancer aggressiveness among AAs. Future studies should further examine the relationship of these SNPs with prostate cancer and 25(OH)D in AAs.

Rights

© 2019, Diana Diaz

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