Date of Award

January 2015

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Yong Zhu

Abstract

Background: Prostate cancer is the most common cancer among men, and the incidence is 1.65 times higher in African Americans than Caucasians. The newly discovered PIWI/piRNA pathway, which regulates transposon and gene expression via small non-coding RNAs, has been implicated in certain aspects of cancer etiology. We hypothesize a novel involvement of the pathway via aberrant gene regulation due to sequence variants within piRNAs and test this hypothesis in relation to prostate cancer in both an African American and Caucasian sample. Methods: To interrogate SNPs embedded in piRNA sequences, we utilized genome-wide genotype data to impute 1,000 Genomes SNPs falling within piRNAs. We then tested for associations at these variants in bothe populations, while controlling for appropriate covariates and principal components. The regions encompassing significant SNPs were subsequently fine mapped. Results: In the African American sample one variant falling within a piRNA, rs61101785, was significantly associated with prostate cancer (FDR-p < 0.10). Fine mapping showed this variant to be the peak of an association signal. The variant is absent in the Caucasian sample. Conclusions: We have tested a novel hypothesis for the involvement of PIWI/piRNAs in cancer risk in a cancer estimated to make up 25% of new male cancer cases in 2015. Our results show the potential for a variant within a piRNA to affect cancer risk. Additionally, the risk variant is absent in Caucasians, potentially explaining some of the racial differences in prostate cancer risk.

Comments

This is an Open Access Thesis.

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