We have previously demonstrated a significant association between human herpesvirus 8 (HHV-8) seroprevalence among men with prostate cancer in the Caribbean island of Tobago compared to cancer free men. HHV-8 DNA has been detected in semen and prostatic tissues in some, but not all reports. I have performed immunohistochemistry (IHC) on prostate tissues from HHV-8 seropositive men from the United States and Tobago with prostate cancer for the expression of viral proteins and determined if expression of these proteins are associated with increased inflammation. My results demonstrate the presence of viral proteins in prostates from seropositive men and among tissues expressing these viral proteins, there is increased inflammation as measured by macrophage infiltrate. I have also looked for the presence of polymorphisms in several genes previously associated with increased risk of prostate cancer to determine if there was a genetic link with the greater risk for prostate cancer in Tobago. We have found single nucleotide polymorphism in the IL-6 gp130 signaling receptor that is associated with increased prostate cancer risk among HHV-8 seropositive men. The public health relevance observed by these results suggests an interaction between HHV-8 infection, increased inflammation and genetic polymorphisms resulting in increased prostate cancer risk. I hypothesize that HHV-8 is a cofactor for prostate cancer in Tobago by establishing a chronic infection which leads to chronic inflammation and ultimately prostate cancer.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-06112008-145438 |
| Date | 28 September 2008 |
| Creators | Montgomery, Jill Deann |
| Contributors | Joel B. Nelson M.D., Frank J. Jenkins, Ph.D., Todd A. Reinhart, Ph.D, Clareann H. Bunker, Ph.D. |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-06112008-145438/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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