Characteristics of 547 pedigrees from the Prostate Cancer Risk Assessment Program over a 10-year period

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Background: Men with a family history (FH) and African American (AA) men are at increased risk for prostate cancer (PCA). Risk assessment for PCA is challenging due to lack of genetic testing. The Prostate Cancer Risk Assessment Program (PRAP) at Fox Chase Cancer Center (FCCC) was established in 1996 to provide screening for men at high risk for PCA and gain insight into familial and genetic patterns of this risk. PCA incidence in PRAP is 9% with an 11% cancer detection rate. Twenty percent of PCA have been found at low PSA values and were Gleason 7 or higher, pointing out the need to gain insight into familial patterns of PCA in these high-risk families for effective risk assessment. Here, we report the prospective data on 547 pedigrees of men in PRAP. Methods: Eligibility criteria for PRAP include any man between 35-69 years with (1) at least 1 first-degree (FDR) with PCA, (2) at least 2 second-degree relatives (SDR) with PCA on the same side of the family, (3) any AA man regardless of FH, or (4) any man with a known BRCA1 or 2 mutation. FH information was self-reported by participants. Imputed individuals were added by data management staff in order to complete a mother-father link for any child reported. Description of relationships captured was performed using the FCOR program in S.A.G.E. 3.1. Frequency and univariate methods (SAS version 9.1) were used for other data analyses. Results: FH information was provided by 88.7% of PRAP men representing 547 unique pedigrees, and 6.96% mother/father imputations were performed to maintain pedigree structure. Approximately 14.8% of males > 18 years have PCA in these families, and 12.6% of the probands have a strong familial risk for PCA (1 FDR and >2 SDR on the same side of the family). Twelve percent of unaffected PRAP probands have pedigrees demonstrating familial PCA, and almost 6% of AA probands report a FH consistent with familial PCA. Furthermore, 20% of unaffected PRAP probands have >1 brother affected with PCA, of which 33% are AA. The most common other cancers found in PRAP families with PCA are breast and colon cancer. Eleven percent of PRAP pedigrees with prostate and any other cancers are of AA ethnicity. Conclusions: This is the first report of familial characteristics in a large, prospectively screened population of men at high-risk for PCA. Familial PCA is quite prevalent in men at high-risk, including AA men. PCA risk assessment measures are greatly needed for early detection of PCA to reduce mortality in this high-risk population.