MOLECULAR BIOMARKERS FOR PROSTATE CANCER SUSCEPTIBILITY

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Prostate cancer is a major public health problem, affecting an estimated one in five American men. However, little is known about the causes of prostate cancer. Aside from the well established risk factors (age, race and family history) suggestive evidence for dietary fat intake exists but is yet inconclusive. Prostate cancer incidence increases with advancing age, it is imperative therefore that we improve our understanding of the underlying mechanisms that dictate the development and progression of prostatic disease. Efforts to understand such mechanisms are hampered by the lack of adequate molecular and genetic markers associated with prostate carcinogenesis, tumor progression and metastasis. In this pilot study we will use complementary molecular biomarkers of exposure (DNA adducts), effect (cytogenetic end-points) and susceptibility (interindividual variation in DNA repair capacity) in the peripheral blood lymphocytes of patients with prostate cancer and controls in an attempt to better understand the mechanism of development of prostate cancer. Our hypothesis is that individuals with altered DNA repair capacity and for elevated levels of DNA adducts, will harbor sufficient amount of numerical and structural chromosome damage that will allow the neoplastic transformation. We will test our hypothesis in 100 cases with prostate cancer and 100 healthy matched controls. In this study we will 1) characterize the role of chromosomal instability, 2) access the DNA damage and repair capacity and 3) compare the DNA adduct levels in background and mutagen induced blood cultures from the prostate cancer patients and controls. We will also determine the association between these biomarkers and the risk to prostate cancer with adjustment for other known epidemiological risk factors, which may have an effect on the background genetic instability. The results of this pilot study will help validate the usefulness of this comprehensive approach in large scale epidemiological studies in the future.