Abstract
Background: Prostate cancer screening with PSA has decreased the average age of prostate cancer detection and increased the number of men who undergo prostate biopsies. Currently two thirds of the prostate biopsies performed due to a high PSA test are negative for prostate cancer leading to unnecessary expense and distress for the individual. One way to decrease the unnecessary procedures associated with PSA screening would be to identify individuals who are either at increased or reduced risk of prostate cancer using newly discovered genetic and environmental risk factors. Aims: Using the males in the Personalized Medicine Research Project (PMRP) population that have had a PSA test, determine if genetic and environmental factors can be incorporated into the PSA screening model to better discriminate individuals who will have a diagnosis of prostate cancer from those with negative biopsies. Methods: Individuals in PMRP who were diagnosed with prostate cancer (N=466) were compared with the entire Marshfield Clinic population to determine cancer screening characteristics such as rate of PSA screening and average age at cancer diagnosis. All men in PMRP who have had a PSA test (N=4659) were genotyped for at least 12 polymorphisms that have been associated with prostate cancer in GWAS studies and dietary history was collected if available. Results: Individuals diagnosed with prostate cancer in the PMRP population tend to have more PSA tests prior to diagnosis than the general population (an average of 7) with 69% (N=320) having at least one PSA test prior to a prostate biopsy. A total of 935 of the 4659 men in the study have had a prostate biopsy with a positive biopsy rate of 34%. Using a panel of 12 previously identified polymorphisms; seven were significantly associated with prostate cancer in our population. Individuals with 1 or fewer risk alleles (15.6% of the population 146 of 935) were less likely to have a diagnosis of prostate cancer on biopsy (OR 1.6). Conclusions: The PMRP population that has experienced at least one PSA screen is a viable population for testing new screening algorithms that incorporate genetic and environmental factors for better identification of prostate cancer risk.
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