NSAIDS and Other Medications in Prostate Cancer Etiology

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Prostate cancer is the most common malignancy in men, yet its etiology remains obscure. A central theme of the carcinogenic process is uncontrolled cell growth, which is a disturbance in the balance between cell proliferation and cell death. Factors that stimulate cell proliferation enhance the opportunity for accumulation of random genetic errors and emergence of a malignant phenotype. Factors that block apoptosis, which would normally remove DNA-damaged cells from the cycle, may promote continued growth of malignant cells. There is compelling evidence that certain medications may act as risk or protective factors for prostate cancer through a common biological pathway involving altered rates of prostatic cell growth or death. To study the relationships between these frequently used medications and prostate cancer, we propose a population-based case-control study of 1000 cases and 1000 controls, aged 40-74 years, that will test the following hypotheses: 1. Use of nonsteroidal anti-inflammatory drugs is associated with a reduced risk of prostate cancer; 2. Use of statins is associated with a reduced risk of prostate cancer; 3. Use of calcium-channel blockers is associated with an increased risk of prostate cancer; and 4. Use of histamine H2-receptor antagonists is associated with an increased risk of prostate cancer. We also will assess genetic polymorphism in the CYP2C9 gene, which is involved in drug metabolism. Logistic regression models will be used to estimate relative risks of prostate cancer associated with use of each type of medication, adjusting for potential confounding factors. Tumor stage and grade will be used to assess whether associations vary by disease aggressiveness. Given the rising frequency of exposure to some of these medications, the information from this study will be timely and is urgently needed. Results of the study may provide unique insights on the pathogenesis of this complex disease and lead to innovative strategies for prostate cancer prevention.