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Novel dimensions in a fluid genome : an integrative risk analysis for cancers of the bladder and breast / by Asaf Wyszynski.

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Author	Wyszynski, Asaf.
Title	Novel dimensions in a fluid genome : an integrative risk analysis for cancers of the bladder and breast / by Asaf Wyszynski.
Date	2014
Abstract	The present thesis is focused on developing a better understanding of factors driving disease biology and overall risk using cancers of the bladder and breast as model systems. As no single approach was likely to unravel the complexities of these conditions alone, we approached the problem from several viewpoints and applied these findings to an updated understanding of disease risk. In Chapter 1, we investigated the influences of modifiable lifestyle and environmental factors, specifically, adiposity and cigarette smoking, on bladder cancer recurrence in a cohort recruited from the local New Hampshire population. In Chapter 2, we further extended these findings within the same cohort to identify the impact of genetic variation in genes involved in nine major carcinogenic processes using a custom SNP array and employed a multifactor dimensionality reduction algorithm to identify epistatic interactions associated with poor prognostic outcomes. In chapter 3, we expand our analyses to examine a novel intergenic polymorphism and its influence on gene expression through distal chromatin interactions as well as characterized its association with breast cancer in 1,182 cases and 1,362 controls, and replicated our findings in an independent set of 62, 533 cases and 60,966 controls. In chapter 4, we utilized both computational approaches and direct biochemical assays to highlight the utility of association studies in revealing novel biological processes, explored a mechanism for direct ER[alpha]-mediated transcriptional repression genome-wide, and identified a putative mediator for targeting this repressive machinery to target loci. The contributions of these findings to the field and the potential ramifications for future investigation are discussed herein.
Description	xi, 178 leaves : ill. (mostly col.)
Format	application/pdf
College	Dartmouth College. Experimental and Molecular Medicine Program. NhDDartmouth Medical School.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.1279

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Novel dimensions in a fluid genome : an integrative risk analysis for cancers of the bladder and breast / by Asaf Wyszynski.

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