RISK FACTORS FOR PROSTATE CANCER PROGRESSION

Abstract

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.