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THE ROLE OF STEROID HORMONES IN THE ETIOLOGY OF UROLOGIC DISEASES
by
Carol Ann Davis-Dao
______________________________________________________________
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements of the Degree
DOCTOR OF PHILOSOPHY
(EPIDEMIOLOGY)
May 2011
Copyright 2011 Carol Ann Davis-Dao
Object Description
| Title | The role of steroid hormones in the etiology of urologic diseases |
| Author | Davis-Dao, Carol Ann |
| Author email | caroldav@med.usc.edu; lorac2201@yahoo.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Epidemiology |
| School | Keck School of Medicine |
| Date defended/completed | 2010-12-15 |
| Date submitted | 2011 |
| Restricted until | Unrestricted |
| Date published | 2011-02-07 |
| Advisor (committee chair) | Cortessis, Victoria K. |
| Advisor (committee member) |
Azen, Stanley Paul McKean-Cowdin, Roberta Siegmund, Kimberly D. Coetzee, Gerhard A. |
| Abstract | One of the main goals of my doctoral training has been to gain experience working with a variety of types of epidemiologic data. The three projects that compose this dissertation have provided me with the opportunity to work with several different data structures: (1) published summary data, (2) population-based family data, (3) prospective cohort data, and (4) population-based case-control data.; For my dissertation, I have employed each of these data structures to investigate the role of steroid hormones in the etiology of several urologic diseases. In the last several decades of epidemiologic research, it has become clear that steroid hormones are involved in many disease processes. For my research, I have studied the relationships between steroid hormone exposure and molecules of steroid hormone response and female bladder cancer, as well as two male urologic diseases: infertility and testicular germ cell tumors.; In my first paper, I investigated the association between male infertility and a polymorphic CAG repeat tract in the androgen receptor gene (AR) through the meta-analysis of a large body of existing literature on the topic. I quantitatively summarized 33 studies, and found that infertile male cases had statistically significantly longer mean CAG repeat length than controls (SMD: 0.19, 95% CI: 0.09-0.29). Meta-analysis of a select subset of 13 studies that used more stringent case and control selection criteria revealed a larger difference between cases and controls (SMD: 0.31, 95% CI: 0.14-0.47). This meta-analysis provides support for an association between increased androgen receptor CAG length and idiopathic male infertility, and brings together for the first time results from many published reports on this topic.; In my second paper, I expanded upon the results of the meta-analysis to conduct an original data analysis studying the association between androgen receptor CAG repeat length and risk of testicular germ cell tumors. Increasing rates of testicular germ cells tumors (TGCTs) over the last 40 years suggest environmental factors are involved in disease etiology, but familial risk studies indicate that genetic factors are also important.; I investigated whether variation in CAG trinucleotide repeat length in exon 1 of the androgen receptor gene is associated with TGCTs using data from a population-based family study. Analyses of 273 TGCT case-mother pairs revealed no association between androgen receptor CAG repeat length and overall risk of TGCTs. Risk of seminoma was significantly associated with shorter CAG repeat length, and the trend was highly significant over decreasing CAG repeat length (CAG ≥20 versus CAG ≤19: OR=0.54 (95% CI: 0.31-0.93), p trend=0.003). Case-case analyses comparing seminoma cases to nonseminoma and mixed germ cell tumors confirmed that seminoma cases had shorter CAG repeat length than other histologies (CAG ≥20 versus CAG ≤19: OR=0.54 (95%CI: 0.29-1.01), p trend=0.003).; My findings indicate that the AR may be involved in progression from CIS to seminoma and that genetically-determined differences in androgen action may be involved in TGCT etiology. These results suggest further work on the role of the androgen receptor in carcinoma in situ cells, and investigation of potential gene-environmental interactions between AR variants and hormonally active agents that may together influence TGCT risk.; In my third paper, I changed my focus from male reproductive disorders, and investigated the role of hormones in the etiology of female bladder cancer. It is known that men have two-to-four times the rate of bladder cancer of women, and this difference in risk cannot be fully explained by known bladder cancer risk factors. Hormones provide an intriguing research area due to the fundamental hormonal differences between men and women, and biological evidence of the effect of steroid hormones on bladder carcinogenesis. Investigating factors that reflect hormone levels among women, including parity, age at menarche, age at menopause and use of exogenous hormones, provides an avenue to study the hypothesis that steroid hormones are associated with risk of bladder cancer.; I analyzed data from women participating in two population-based studies: the Los Angeles-Shanghai Bladder Cancer Study, in which 349 female case-control pairs were enrolled in Los Angeles and 131 female cases and 138 frequency-matched controls were enrolled in Shanghai; and the California Teachers Study (CTS), in which 196 incident cases of bladder urothelial carcinoma were diagnosed between 1995 and 2005 in an analytic cohort of 120,857 women. I also conducted a meta-analysis summarizing data on these associations from our primary analyses together with results in the published literature.; In primary data analyses, parous women experienced at least a 30% reduced risk of bladder cancer compared with nulliparous women (Shanghai: OR=0.38, 95%CI: 0.14-1.07; CTS: RR=0.69, 95%CI: 0.50-0.95) consistent with results of a meta-analysis of nine studies (summary RR=0.73, 95%CI: 0.63-0.85). The CTS, which included data on formulation of menopausal hormone therapy (HT), revealed a protective effect for use of combined estrogen and progestin compared with no HT use (RR=0.60, 95%CI: 0.37-0.98). Meta-analysis of three studies provided a similar effect estimate (summary RR=0.65, 95%CI: 0.48-0.88).; These results suggest that hormonal and reproductive factors influence risk of female bladder cancer, and that processes mediated by steroid hormones may be important determinants of the gender disparity in bladder cancer rates. |
| Keyword | hormones; male infertility; testicular germ cell tumors; bladder cancer |
| Geographic subject (city or populated place) | Shanghai |
| Geographic subject (county) | Los Angeles |
| Geographic subject (state) | California |
| Geographic subject (country) | China |
| Coverage date | 1995/2005 |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m3644 |
| Contributing entity | University of Southern California |
| Rights | Davis-Dao, Carol Ann |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | cisadmin@lib.usc.edu |
| Filename | etd-DavisDao-4256 |
| Archival file | uscthesesreloadpub_Volume32/etd-DavisDao-4256.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | THE ROLE OF STEROID HORMONES IN THE ETIOLOGY OF UROLOGIC DISEASES by Carol Ann Davis-Dao ______________________________________________________________ A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements of the Degree DOCTOR OF PHILOSOPHY (EPIDEMIOLOGY) May 2011 Copyright 2011 Carol Ann Davis-Dao |
