Lloyd, Stacy Monique
(2010)
An Analysis of Estrogen Metabolism and Breast Cancer Risk.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Breast cancer is the most common noncutaneous form of cancer among women in the US. In recent years, the overall mortality rate has declined, yet there still exists a significant racial disparity in the incidence and mortality between African American and Caucasian women. While numerous hypotheses have been proposed to explain this difference, few offer a biological explanation.There is a well established association between estrogens and breast cancer risk, and the ratio of two estrogen metabolites, 2-hydroxyestrone (2OHE1) and 16á-hydroxyestrone (16OHE1), has been implicated as a marker of breast cancer risk. Many studies have also assessed the relationship between endogenous estrogens and mammographic density. Mammographic density is one of the strongest predictors of breast cancer risk, but the mechanism by which it influences this risk remains unknown. Nonetheless, few have examined mammographic density in relation to the 2OHE1:16OHE1 estrogen metabolite ratio (EMR).Research suggests that the Cytochrome P450 1B1 (CYP1B1) gene may also mediate breast cancer risk, as this gene is very active in estrogen metabolism. In fact, the Leu432Val polymorphism has reportedly been associated with urinary levels of the 2OHE1:16OHE1 EMR.The objective of this study was to investigate some of the relationships found among the 2OHE1: 16OHE1 EMR, CYP1B1 Leu432Val polymorphism, mammographic density, race, and breast cancer risk. The 2OHE1:16OHE1 EMR was associated with both breast cancer risk and the CYP1B1 Leu432Val polymorphism, yet, no association with breast cancer risk and this polymorphism was observed. This suggests that if the CYP1B1 Leu432Val polymorphism alters breast cancer risk, it does so through variations in the 2OHE1:16OHE1 EMR. When taking race into account, no association between mammographic density and the 2OHE1:16OHE1 EMR was observed. In culture, evidence was found to suggest that the 2OHE1:16OHE1 EMR is influenced by subcellular effects or other intrinsic factors (i.e. genetic variation), as passage number was the only significant contributor to the 2OHE1:16OHE1 EMR.The results of this study have great public health significance, as it provides a better understanding of the risk factors, including racial differences, and etiology of breast cancer, which will ultimately lead to better prevention and treatment for all women.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
28 June 2010 |
| Date Type: |
Completion |
| Defense Date: |
30 June 2009 |
| Approval Date: |
28 June 2010 |
| Submission Date: |
12 April 2010 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Human Genetics |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Cytochrome P450 1B1; estrogen metabolites; mammographic density; race |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-04122010-170655/, etd-04122010-170655 |
| Date Deposited: |
10 Nov 2011 19:36 |
| Last Modified: |
15 Nov 2016 13:39 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/7073 |
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