Molecular Epidemiologic Case-Case Study of Prostate Cancer Susceptibility

摘要

Although prostate cancer is the most common cancer in western countries, risk factors for this disease have not been well characterized. This study builds upon an ongoing project by adding genetic susceptibility markers. Additionally, we are accruing 100 new patients with metastatic disease, Constitutional markers are being evaluated as predictors of prostate cancer risk including: (a) polymorphisms within the androgen receptor and 5-alpha-reductase genes, (b) relative expression levels of several mismatch repair genes (hMSH2 and hMLH1) and radiosensitivity related genes (ATM, GADD45, XRCC1), and (c) frequency of replication errors in tumor and normal DNA. These data will be integrated with epidemiologic and clinical information. Results from this research may identify markers of progression, which could help in the diagnosis and treatment of prostate cancer. Our preliminary findings indicate that decreased mismatch repair gene expression may be associated with increased risk of prostate cancer. These results suggest that DNA damage-repair pathways may be involved in prostate carcinogenesis. Incorporation of more data from this study, including the metastatic patients, will allow us to confirm this finding and further explore the molecular basis of the underlying mechanisms of prostate cancer etiology.