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GENES AND HORMONAL FACTORS INVOLVED IN THE DEVELOPMENT
OR RECURRENCE OF BREAST CANCER
by
Eunjung Lee
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(EPIDEMIOLOGY)
May 2008
Copyright 2008 Eunjung Lee
Object Description
| Title | Genes and hormonal factors involved in the development or recurrence of breast cancer |
| Author | Lee, Eunjung |
| Author email | leee@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Epidemiology |
| School | Keck School of Medicine |
| Date defended/completed | 2008-02-26 |
| Date submitted | 2008 |
| Restricted until | Restricted until 16 Apr. 2010. |
| Date published | 2010-04-16 |
| Advisor (committee chair) | Ursin, Giske |
| Advisor (committee member) |
Hill, Colin Haiman, Chris Stram, Dan McKean-Cowdin, Roberta |
| Abstract | BRCA1 and BRCA2 (BRCA1/2) genes are well-established breast cancer susceptibility genes. A large number of variants in these genes has been reported, including variants with clearly deleterious effects and variants with unknown significance on breast cancer risk. Classification of such unclassified variants (UVs) is an area of growing interest, but no study has systematically assessed whether the various classification methods are biologically meaningful. Further, given that not all BRCA1/2 deleterious mutation carriers develop breast cancer, environmental modifiers of breast cancer risk in BRCA1/2 mutation carriers need to be identified. In this dissertation, I present results from a population-based case-control study of young breast cancer patients to investigate these issues.; In my first paper, I used sequencing data of BRCA1/2 genes in 1,469 breast cancer patients. There were 262 distinct BRCA1/2 variants, including 147 UVs. Application of various methods to classify each variant showed that the BRCA1 UV carriers, but not BRCA2 UV carriers, who were classified as 'high risk' using each classification method were more likely to have a family history than those classified as 'low risk'.; In a second paper, I examined potential modifiers of the effect of BRCA1/2 on breast cancer risk. An increasing number of full-term pregnancies was associated with a decreased breast cancer risk, regardless of BRCA1/2 status. Breastfeeding was protective in the BRCA1/2 mutation non-carriers but not in the carriers. OC use overall was not associated with risk of breast cancer, regardless of BRCA1/2 status.; There is a critical need for a new prognostic and predictive marker of breast cancer treatment. Additional work to investigate treatment outcome of BRCA1/2 mutation carriers would have been an important next step in this population-based sample of young breast cancer patients, but survival and treatment data of this study population were not collected. However, in the third paper of my dissertation, I explored the question of treatment response in a separate breast cancer population with regard to 78kD glucose-regulated protein (GRP78), which has been shown to confer chemoresistance to human breast cancer cells. Our results from a retrospective cohort of 127 breast cancer patients treated with adriamycin-based chemotherapy showed that GRP78 positive expression, evaluated by immunohistochemistry, was associated with a shorter time to recurrence (HR=1.78; p=0.16). Interestingly, our subgroup analyses showed that there is a potential interaction between GRP78 and taxane-addition. The use of GRP78 as a predictor for chemoresponsiveness warrant larger studies. |
| Keyword | breast cancer; GRP78; oral contraceptives; reproductive factors; unclassified variants; BRCA |
| 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 |
| Type | texts |
| Legacy record ID | usctheses-m1134 |
| Contributing entity | University of Southern California |
| Rights | Lee, Eunjung |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Lee-20080416 |
| Archival file | uscthesesreloadpub_Volume44/etd-Lee-20080416.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Full text | GENES AND HORMONAL FACTORS INVOLVED IN THE DEVELOPMENT OR RECURRENCE OF BREAST CANCER by Eunjung Lee A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (EPIDEMIOLOGY) May 2008 Copyright 2008 Eunjung Lee |
