Date of Award

5-2008

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program

Nursing

Research Advisor

Ann K. Cashion, PhD

Committee

Carolyn Driscoll, PhD Pamela Hinds, PhD Melissa Hudson, MD Geoffrey Neale, PhD Mary Relling, PharmD

Keywords

Late effects, Hodgkin Lymphoma, secondary breast cancer, gene expression, single nucleotide polymorphism, copy number variation

Abstract

dentification of genetic risk factors associated with the development of secondary cancers would facilitate identification of at risk patients and permit modification of therapy and heightened surveillance that may reduce cancer-related morbidity and mortality. Women survivors of pediatric Hodgkin lymphoma (HL) have an increased risk of morbidity and mortality associated with secondary effects of therapy, with a 35-75 fold excess risk of developing breast cancer over the general population. The mechanism for secondary breast cancer among Hodgkin survivors is not understood. Researchers have postulated that the familial characteristics of HL could be associated with mutations found within familial cancer syndromes; however, these mutations have not been identified. This has led to the exploration of inherent polymorphisms that might impair the patient’s capability to detoxify chemotherapy and/or repair DNA damage produced by irradiation. Examinations of candidate polymorphisms indicate that single nucleotide changes may have only a small effect on the development of subsequent cancers. However, multiple studies support the idea that sensitivity to irradiation and the subsequent development of breast cancer is mediated through the interaction of multiple genes or gene complexes. The objective of this case-control study design was to explore the identification of potential candidate genes and polymorphisms that may be risk factors for the development of secondary breast cancer among women who are pediatric HL survivors. Global gene expression and genotyping of women with (n=13) and without (n=36) secondary breast cancer after the treatment of pediatric HL were compared. Differences were found in global gene expression and genotyping between the cases and controls. Additionally, copy number variation in association with gene expression found a locus of interest at 15q11.2 in association with the development of secondary breast cancer.

DOI

10.21007/etd.cghs.2008.0197

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