Author ORCID Identifier

0000-0001-6647-2025

Date of Graduation

12-2017

Document Type

Dissertation (PhD)

Program Affiliation

Human and Molecular Genetics

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Dr. Xifeng Wu

Committee Member

Dr. Powel Brown

Committee Member

Dr. Huamin Wang

Committee Member

Dr. Michelle Hildebrandt

Committee Member

Dr. Yuanqing Ye

Abstract

Quality of life (QOL) is an independent prognostic factor for cancer. Lung cancer is the leading cause of cancer death. Breast cancer is the most diagnosed. Bladder cancer is the most expensive cancer to treat because of its high recurrence rate. We set to perform comprehensive analyses of predictors of QOL in these cancer sites with the future goal of improving QOL and outcomes.

In 6,456 newly diagnosed lung cancer patients, we investigated the relationship between baseline patient characteristics and QOL to identify determinants of QOL. A QOL questionnaire (SF-12v1) measured patients’ physical component summary (PCS) and mental component summary (MCS). Factors that were associated with mean PCS and MCS included smoking status (PCS PtrendtrendtrendtrendMEF2B: rs2040562 showed an increased risk of poor MCS (OR: 3.06, 95% CI: 1.05-8.92, P=0.041).

Next, in 10,681 newly diagnosed breast cancer patients, we found that physical QOL was associated with higher risks of recurrence and death. We identified determinants of QOL such as marital status and tumor size. We found that Hispanics and Blacks reported lower PCS and the determinants of poor QOL were disproportionally more common in minorities.

Finally, we investigated the associations between genetic variants in the dopaminergic pathway and clinical outcomes in bladder cancer patients. This pathway is closely related to depression (a QOL domain) and depressive symptoms at diagnosis are associated with bladder cancer mortality. Using a two-stage design (discovery and independent validation), we identified several single nucleotide polymorphisms (SNPs) that was associated with recurrence or progression in non-muscle invasive bladder cancer overall or stratified by treatment.

In conclusion, we found important determinants of QOL in breast and lung cancer patients and racial disparities in breast cancer patients’ QOL. This may contribute to racial disparities in breast cancer outcomes. Genetic variations in QOL-related pathways may modulate bladder cancer outcomes. These results provide a framework for identifying cancer patients at high risk for poor QOL and poor clinical outcomes.

Keywords

Quality of Life, Lung Cancer, Breast Cancer, Bladder Cancer, Single Nucleotide Polymorphisms, Cancer Clinical Outcomes

Available for download on Monday, June 11, 2018

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