Hoffman, Linda J.
(2005)
Sero-Epidemiological Studies on Human Herpes Virus-8.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Human herpes virus-8 (HHV-8) is a known carcinogenic agent. This report investigates five populations to determine if HHV-8 was associated with disease onset. Detection and levels of antibodies were measured using an enhanced immunofluorescent assay and were analyzed with the statistical program, SPSS.In the first study, we tested the hypothesis that HHV-8 was the causative agent in Langerhan's cell histiocytosis (LCH). The seroprevalence of HHV-8 among 159 LCH patients was similar to the control group, indicating that HHV-8 is not the etiological agent of LCH.In the second study, we tested the hypothesis that HHV-8 reactivation occurs in solid-organ transplant (SOT) patients, following immunosuppression. We found a significant increase in HHV-8 seropositivity when comparing pre-transplant to post-transplant samples (p-less than .01). There was also an overall increase in viral antibody titers following transplantation (p=less than .001), indicating viral reactivation. In the third study, we compare the SOT results to bone-marrow transplant patients (BMT). Longitudinal serum samples from 34 BMT patients did not demonstrate a significant association with HHV-8 as compared to the control (p=.716) or the SOT populations (p=.180). In addition, HHV-8 reactivation did not occur post-transplantation.In the fourth study, we tested the hypothesis that HHV-8 is associated with increased risk of prostate cancer (PrCa). There was greater than a 2-fold association between HHV-8 seroprevalence and PrCa among African-Caribbean men from Tobago (p=.003). A similar trend was present in a PrCa cohort from the United States, p=greater than .05.In a fifth study, we tested the hypothesis that HHV-8 increased the risk of PrCa among men who carried genetic polymorphisms in the androgen (AR) and estrogen receptor (ESR1) genes. This study analyzed an expanded Tobago cohort, which demonstrated an association between HHV-8 and PrCa (OR 1.74, p=.032). An increased association was found among seropositive men carrying the high-risk AR allele (OR=2.46, p=.023) and ESR1 allele (OR=3.10, p=.004). The strongest association was found in seropositive men with both high-risk alleles (OR=5.20, p=.017).This study demonstrates the use of HHV-8 serology as a marker for an increased public health cancer detectable risk, due to viral prevalence or reactivation.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
9 June 2005 |
| Date Type: |
Completion |
| Defense Date: |
20 December 2004 |
| Approval Date: |
9 June 2005 |
| Submission Date: |
13 April 2005 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Infectious Diseases and Microbiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
cancer; carcinogenic; herpesvirus; Human herpesvirus-8; KSHV; epidemiology; HHV-8; public health |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-04132005-195044/, etd-04132005-195044 |
| Date Deposited: |
10 Nov 2011 19:36 |
| Last Modified: |
15 Nov 2016 13:40 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/7095 |
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