Gene Expression and Fatigue in Puerto Rican Men
Issue Date
2015-05-31Author
Gonzalez, Velda Janet
Publisher
University of Kansas
Format
229 pages
Type
Dissertation
Degree Level
Ph.D.
Discipline
Nursing
Rights
Copyright held by the author.
Metadata
Show full item recordAbstract
Background: Prostate cancer is the most frequently diagnosed cancer in men (40.6% in 2010) in Puerto Rico and external beam radiation therapy (EBRT) is the preferred form of treatment for one third of newly diagnosed prostate cancer patients in Puerto Rico. Puerto Ricans often experience ethnic disparities in cancer treatments and in their symptom experience. Purpose: This study will: (a) describe the trajectory of fatigue among Hispanic Puerto Rican men over the course of receiving EBRT for non-metastatic prostate cancer and compare these findings with historical data of fatigue symptoms of Caucasian men with prostate cancer during EBRT; (b) assess gene expression changes from baseline to midpoint of EBRT using microarray technology; and (c) determine the association between changes in genes expression and changes in fatigue score from baseline to midpoint of EBRT using an unbiased, hypothesis-generating approach. Methods: As a prospective exploratory and comparative design study, fatigue was measured using the Functional Assessment of Cancer-Therapy –fatigue from 26 Hispanic Puerto Rican men who were newly diagnosed with non-metastatic prostate cancer at three time points (baseline [prior to EBRT], midpoint [days 19-21], and end of EBRT [days 38-42]). Whole-blood samples also were collected at baseline and at midpoint of EBRT to explore the differential expression of genes using microarray. Functional networks of the differentially expressed genes were examined. Descriptive data were analyzed using t-test, Wilcoxon, and Friedman test for repeated measures. Gene expression data were analyzed using the LIMMA package in R and the functional network analysis was conducted using Ingenuity Pathway analysis. Findings: Subjects were ages 52-81 with fatigue scores that were unchanged during EBRT (baseline= 42.38, SD= 9.34; mid-point=42.11, SD= 8.93, endpoint= 43.04, SD= 8.62); Friedman's test: χ21.20[df, 2], p=.55). Three hundred seventy-three genes (130 up regulated and 243 down regulated) were differentially expressed from baseline to mid-point of EBRT (FDR<0.01). The top distinct canonical pathways of the differentially expressed probesets (p< 0.0001) were: Phospholipase C Signaling, Role of NFAT in Regulation of the Immune Response, and Gαq Signaling. Conclusions: There were no changes in fatigue scores among Puerto Rican men during EBRT for prostate cancer. However, differentially expressed genes during EBRT suggest activation of immune response, which is a mechanism proposed to explain cancer-related fatigue. Further investigation is warranted to explain the disparity in fatigue symptoms reporting of Puerto Rican men from other ethnicities receiving the same treatment.
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