This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The purpose of the study is to investigate the effect of feeding a high fat, high sugar diet on serum prostate specific antigen (PSA) in cynomolgus monkeys. Thirty cynomolgus monkeys will be fed a high fat, high sugar diet for 12 months. Prostate cancer is the most common non-cutaneous cancer in American men. It is estimated that more than 234,000 cases are diagnosed annually resulting in 27,000 deaths. A major characteristic of normal prostate cells and prostate cancer cells is selective production of PSA. The main function of PSA is to liquefy the seminal plasma clot after ejaculation. Normally PSA is restricted to the prostate gland and its secretions and very little is present in the blood stream. However, PSA is released at increased levels into the blood early in the development of prostatic diseases and therefore is widely used for screening, diagnosing and monitoring of prostate cancer, although it is also elevated in other disorders. Serum PSA level is the most widely used clinical biomarker for any cancer with about 45 million serum PSA tests performed per year worldwide. The use of PSA screening has resulted in a decline in both prostate cancer mortality and the incidence of metastases at the time of diagnosis. However, PSA has clinically meaningful limitations as a screen for prostate cancer due to its low sensitivity and specificity. Only 25-30% of men with elevated PSA ( 4ng/?l) actually have cancer, and in addition, some men with cancer do not show elevated PSA. Added to this complexity is the finding that overweight men tend to exhibit lower PSA values than men of normal weight. The reason for this reduction in PSA with obesity is not understood, but the result is that overweight men have higher mortality due to prostate cancer, higher Gleason scores at diagnosis and respond to treatment poorly. The uncertainty in the interpretation of serum PSA levels is a major clinical concern. There is significant need for more information on the causes of individual variation in PSA levels among men at risk for prostate cancer. There is also a need to understand PSA biology as it may be more than a marker for prostate cancer but may actually be important in the disease process. The long-term goal of this line of research is to develop a nonhuman primate model for the study of the biology of PSA, and to use that model to investigate the various causes of individual variation in serum PSA levels that are not due to cancer itself. The known (non-cancer) causes of variation in serum levels of PSA include genetic differences among men, obesity, and possibly diet separate from obesity. In order to pursue larger external funding for analyses of the relationships among diet, obesity, adiposity and serum PSA in an appropriate nonhuman primate model, we need adequate preliminary data demonstrating that 1) we can reliably measure serum PSA in a given species, 2) the serum PSA levels in that species are negatively correlated with obesity, adiposity or BMI, and 3) we can manipulate diet and adiposity in order to experimentally control these variables and thus investigate the mechanisms through which diet or obesity influence PSA. The outcome of this pilot study will be novel information on the effect of this diet on serum PSA levels in cynomolgus monkeys. Documentation of this relationship will allow us to propose larger more detailed studies of the effect of diet, adiposity, obesity on serum PSA in nonhuman primates. This pilot study will specifically address the issue of why PSA levels are lower in obese individuals yet it has been reported that prostate cancer risk is increased with obesity. The results from this project will give answers to the current dilemma in the prostate cancer field that indicates that obese men have low serum PSA despite having higher prostate cancer mortality rates.
Showing the most recent 10 out of 444 publications
