Objectives Genetic studies of familial prostate cancer, which is often asymptomatic until advanced stages, rely on correct designation of affection status. In this pilot study, we set out to determine the proportion of unaffected men whose families are participating in a study of hereditary prostate cancer who have been tested for prostate cancer with serum prostate-specific antigen (PSA) measurement and digital rectal examination (DRE). Methods Participants were identified from the University of Michigan Prostate Cancer Genetics Project, a family-based study of inherited prostate cancer susceptibility. Of the 141 eligible affected and unaffected sons of men with prostate cancer, 124 (88%) completed a mailed questionnaire regarding serum PSA testing and DRE history. Results Among unaffected men, 95% reported ever having had a PSA test, and 97% ever having had a DRE, with most initial tests occurring between the ages of 40 and 60 years. No significant difference in the mean age at first PSA test or DRE between the affected and unaffected men was observed. Affected men were significantly more likely than unaffected men to have a first PSA level greater than 2.5 ng/mL (P = 0.006), but not greater than 4.0 ng/mL (P = 0.614). Conclusions Most men with a family history of prostate cancer are undergoing early detection testing. The differences in early detection testing practices do not appear to account for the difference in affection status among the sons of men with prostate cancer.

A recent study of hereditary prostate cancer has provided evidence for a prostate cancer-susceptibility locus, HPC20, which maps to 20q13. To assess further the potential contribution of this locus to prostate cancer susceptibility, we studied 172 unrelated families affected by prostate cancer, using 17 polymorphic markers across a 98.5-cM segment of chromosome 20 that contains the candidate region. Parametric analysis, allowing for heterogeneity, resulted in an overall HLOD score of 0.09 (P=.39) at D20S171, under the assumption of linkage in 6% of families. Mode-of-inheritance-free analysis of the entire data set resulted in a maximal Zlr score of 0.76 (LOD 0.13; P=.22) at the same location. The strongest evidence for linkage was seen in the subset of 16 black families (LOD 0.86; Zlr=1.99; P=.023) between markers D20S893 and D20S120, near the putative location of HPC20. Although some positive results were observed, our linkage study does not provide statistically significant support for the existence of a prostate cancer-susceptibility locus HPC20 at 20q13.

Several genetic epidemiological studies have provided data to support the hypothesis that there are genes on the X chromosome that may contribute to prostate cancer susceptibility. A recent linkage study of 360 prostate cancer families described evidence for a prostate cancer predisposition gene, termed HPCX, which maps to Xq27-28. To confirm the potential contribution of this locus to prostate cancer susceptibility in an independent dataset, we studied 153 unrelated families who are participants in the University of Michigan Prostate Cancer Genetics Project. Families selected for this analysis have at least two living family members with prostate cancer that are related in a way that they could potentially share a common ancestral copy of an X chromosome. DNA samples were genotyped using a panel of seven polymorphic markers spanning 30 cM and containing the HPCX candidate region. The resulting data were analyzed using both nonparametric and parametric linkage methods. Analysis of all 153 families using multipoint non-parametric linkage (NPL) methods resulted in positive NPL Z-scores across the entire candidate interval (NPL Z-scores of 0.23-1.06, with corresponding one-sided Ps of 0.41 and 0.15, respectively). The 11 African-American families had negative NPL Z-scores across the same 30-cM interval. Analysis of the 140 Caucasian families produced a maximal NPL Z-score of 1.20, with a corresponding one-sided P of 0.12 at marker DXS1113. The subset of families with no evidence of male-to-male disease transmission and with early-onset prostate cancer (average age at diagnosis within a family < or = 65 years) contributed disproportionately to the evidence for linkage for the entire dataset in the HPCX candidate region (near marker DXS1113). In conclusion, this study of 153 families, each with two or more living members with prostate cancer, provides some additional support for the existence of a prostate cancer susceptibility gene at Xq27-28.