Thesis (M.S.)--Rutgers University, 2009. / "Graduate Program in Food Science." Includes bibliographical references (p. 66-74).

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Not available / text

abstract / toc / Physiology / Master / Master of Philosophy

published_or_final_version / Anatomy / Master / Master of Philosophy

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Introduction: This dissertation seeks to identify novel, potentially modifiable risk factors that could be used to reduce the risk of prostate cancer (PCa) progression. Aim 1 investigates the effects of obesity and smoking on PCa progression, aim 2 studies the effects of specific medication use on PCa progression, and aim 3 identifies factors associated with faster PCa progression.Methods: Data from 140 subjects from the Watchful Waiting study followed every 3 months for up to 5 years were used. Multiple linear regressions were used to determine associations with baseline PSA. PSA velocity (rate of change of PSA over time) was used as a surrogate marker for PCa progression. Mixed effect models were used to assess the effect of obesity, smoking and medication use on PSA velocity(aim1 and 2). For aim 3, subjects were categorized as slow, intermediate and fast progressors based on tertiles of PSA velocity. In addition to the above variables, age, Gleason score, chromogranin-A, family history, selenium and free PSA were investigated as determinants of faster PCa progression using multiple logistic regressions. Analyses were run using two models, comparing slow progressors to fast progressors (model1) and slow progressors to a combination of fast and intermediate progressors (model2).Results: Aspirin use was negatively associated with baseline PSA (coefficient = -0.39 and 95% confidence interval (CI):-0.612, -0.158). Aspirin effect was statistically significant in never smokers (coefficient = -0.54, 95% CI: -0.916, -0.170) but not in ever smokers (coefficient = -0.22, 95% CI: -0.505, 0.065). Ever smoking was statistically significantly associated with higher PSA velocity compared to never smoking (coefficient = -0.001, 95% CI: 0.0002, 0.002). In aim 3, pack-years of smoking were positively associated whereas aspirin use was negatively associated with high PSA velocity in both models. Odds Ratio and 95% CI for smoking and aspirin use for model1 and 2 respectively; 1.03 (0.92, 1.13), 1.02 (1.00, 1.03), 0.24(0.06, 0.94) and 0.26(0.10, 0.68).Conclusions: Although more studies are needed before recommendations can be made, if these results are borne to be true in other studies these modifiable risk factors can be potentially be used in prevention of PCa progression.

Prior research has suggested that life style factors, such as diet and physical activity, influence prostate cancer (PCa) progression. Metformin intake has been shown to be associated with decreased cancer risk in type II diabetic patients. We hypothesize that a low carbohydrate diet, prolonged aerobic exercise and metformin treatment can all independently slow prostate tumor development and a combination regimen will have an additive benefit. We used LNCaP xenografts to test this hypothesis. Results revealed that a diet low in carbohydrate reduced food consumption and a combination with exercise significantly reduced animal body weights. Ten weeks of metformin did not significantly alter tumor growth rate compared to control animals. Ten weeks of exercise significantly inhibited tumor growth. Out results suggest that dietary carbohydrate alteration or the administration of metformin alone cannot significantly influence prostate tumor progression. A suitable sustained exercise regimen may offer a more protective effect against PCa progression.

Introduction Prostate cancer (PCa) is the most commonly diagnosed male malignancy and the second leading cause of male cancer death in the Western world. In the United States of America (USA), African American men (AAM) have among the highest rates of PCa in the world. They develop the disease 1.5 times more frequently than European American men (EAM) of the same age .The mortality rate is approximately two to three times higher for AAM compared to EAM. There is a dearth of literature exploring the incidence and treatment outcomes of this disease based on racial profiling in a South African population. This study aims to evaluate racial disparities with a focus on patients with PCa managed in the public health care sector in the province of Kwazulu Natal (KZN). Patients and methods The study was a retrospective analysis of patients with PCa treated at Inkosi Albert Luthuli Central Hospital and Addington Hospital, which are both based in the Durban Metropolitan area in the province of KZN. Data extracted from the folders of patients with PCa who presented between March 2003 and December 2007 were collated onto a data capture form and analysed. Patient data were analysed according to the following categories: „h Patient demographics; „h Patient follow-up period; „h Disease risk profile; „h Response to treatment; „h Compliance on treatment. SPSS version 15.0 was used to analyse the data. Within each disease category, the response variables were analysed by race group using non-parametric Kruskal-Wallis tests. Multiple comparisons were made using pairwise Mann-Whitney tests and Bonferroni adjusted significance levels according to the number of multiple comparisons made. In order to control for other confounding factors such as age, serum PSA levels and compliance, Cox proportional hazards models were used. Hazard ratios and 95% confidence intervals were also reported. Results In KZN, the majority of the population is classified as blacks (82.9%). The Indian population group makes up 9.0% of the provincial population while white and coloured people make up 6.1% and 2.0% of the provincial population respectively. In this study population, Blacks made up 57.7% and whites made up 27.5%, followed by 11.4% of Indians and 3.4% of coloureds. The racial frequency distribution of the study population demonstrated that whites had a higher incidence of PCa when analysing their demographic profile in the province. Blacks had the highest median total serum prostate specific antigen (PSA) levels on presentation. When compared to that of the white study population, this was found to be statistically significant (p < 0.001). There was a significant association between stage of disease and race (p = 0.001). In the black group, a greater proportion had metastatic rather than localised or locally advanced disease, and in the white group the converse was seen, whereas in the Indian and coloured groups an almost equal proportion had localised or locally advanced disease versus metastatic disease. A crude analysis of progression free survival (PFS) data in patients with metastatic disease demonstrated that PFS was significantly (p = 0.003) longer for whites compared to blacks. Cox regression analysis did not confirm the influence of race on disease progression but this was confounded by incomplete data. Discussion The high incidence of whites in our study population relative to their racial distribution in the province may be explained by better educational and awareness levels of PCa and better access to healthcare facilities in this race group as compared to blacks. The data demonstrating a more advanced stage of disease presentation and higher median PSA levels in the black population may be reflective of an informational void on screening and awareness of PCa and/or a more aggressive disease course in this population group. The hypothesis that the black population may have a more aggressive disease course is given further credence by the crude analysis data suggesting a longer PFS for whites when compared to blacks. Conclusions This study invites further exploration of racial trends in PCa incidence, risk profile and outcomes amongst the diverse population groups of SA. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2009.

Prior research has suggested that life style factors, such as diet and physical activity, influence prostate cancer (PCa) progression. Metformin intake has been shown to be associated with decreased cancer risk in type II diabetic patients. We hypothesize that a low carbohydrate diet, prolonged aerobic exercise and metformin treatment can all independently slow prostate tumor development and a combination regimen will have an additive benefit. We used LNCaP xenografts to test this hypothesis. Results revealed that a diet low in carbohydrate reduced food consumption and a combination with exercise significantly reduced animal body weights. Ten weeks of metformin did not significantly alter tumor growth rate compared to control animals. Ten weeks of exercise significantly inhibited tumor growth. Out results suggest that dietary carbohydrate alteration or the administration of metformin alone cannot significantly influence prostate tumor progression. A suitable sustained exercise regimen may offer a more protective effect against PCa progression.