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The Effects of Anthropometry and Angiogenesis on Breast Cancer Etiology

Reeves, Katherine Whitney (2008) The Effects of Anthropometry and Angiogenesis on Breast Cancer Etiology. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Factors such as mammographic breast density and angiogenesis may be related to breast cancer development, though numerous questions about the etiologic mechanisms remain. Percent density is positively associated with breast cancer risk, yet is negatively associated with another breast cancer risk factor, body mass index (BMI). Vascular endothelial growth factor (VEGF) is a primary regulator of angiogenesis, yet its relationship to breast cancer risk is unclear. We evaluated the longitudinal association between BMI and breast density in the Study of Women's Health Across the Nation (SWAN) Mammographic Density Substudy (N=834). Using adjusted random intercept models, changes in BMI were not associated with changes in dense breast area (Beta=-0.0105, p=0.34), but were strongly negatively associated with changes in percent density (Beta=-1.18, p<0.001). Thus, effects of changes in anthropometry on percent breast density may reflect effects on non-dense tissue, rather than on the dense tissue where cancers arise. Breast density was measured from routine screening mammograms which were not timed with SWAN visits. We developed a method to align the off-schedule mammogram data to the study visit times using linear interpolation with multiple imputation. Our method was shown to be valid, with an average bias for dense breast area of 0.11 cm2. In the random intercept models, use of a simple matching algorithm to estimate breast density produced different (Beta=-0.0155, p=0.04), and likely incorrect, results. Our linear interpolation with multiple imputations method may be applicable to other longitudinal datasets with important data collected off-schedule. In a separate case-control study, the Mammograms and Masses Study (MAMS), we evaluated the association between serum VEGF levels and breast cancer (N=407). Geometric mean VEGF levels were higher among cases (331.4 pg/mL) than controls (291.4 pg/mL; p=0.21). In a multivariable logistic regression model, VEGF greater than or equal to 314.2 pg/mL was positively associated with breast cancer (odds ratio 1.37, 95% confidence interval 0.88-2.12), albeit non-significantly. Higher levels of VEGF may increase breast cancer risk. We have identified roles for anthropometry and angiogenesis in breast carcinogenesis. Enhancing knowledge of breast cancer etiology is a significant contribution to public health and may lead to improved opportunities for prevention or early detection.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Reeves, Katherine; katherine.whitney@aya.yale.eduKWR2
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairCauley, Jane A.jcauley@edc.pitt.eduJCAULEY
Committee MemberWeissfeld, Joel L.jwepid@pitt.eduJWEPID
Committee MemberNess, Roberta
Committee MemberStone, Roslyn A.roslyn@pitt.eduROSLYN
Committee MemberVogel, Victor
Date: 23 June 2008
Date Type: Completion
Defense Date: 11 January 2008
Approval Date: 23 June 2008
Submission Date: 12 February 2008
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: angiogenesis; biomarkers; body mass index; Breast cancer; breast density; vascular endothelial growth factor
Other ID:, etd-02122008-075442
Date Deposited: 10 Nov 2011 19:31
Last Modified: 15 Nov 2016 13:36


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