Linkage analyses at the chromosome 1 Loci 1q24-25 (HPC1), 1q42.2-43 (PCAP), and 1p36 (CAPB) in families with hereditary prostate cancer

Recent studies suggest that hereditary prostate cancer (PRCA) is a complex disease, involving multiple susceptibility genes and variable phenotypic ex pression. Through linkage analysis, potential prostate cancer susceptibilit y loci have been mapped to 3 regions on chromosome 1. To investigate the re ported linkage to these regions, we conducted linkage studies on 144 PRCA f amilies by using microsatellite markers in regions 1q24-25 (HPC1) and 1q42. 2-43 (PCAP). We also examined the 1p36 (CAPB) region in 13 PRCA families wi th at least one case of brain cancer. No significant evidence of linkage to the HPC1 or PCAP region was found when the entire data set was analyzed. H owever, weak evidence for linkage to HPC1 was observed in the subset of fam ilies with male-to-male transmission (n = 102; maximum multipoint nonparame tric linkage [NPL] 1.99, P = .03). Weak evidence for linkage with heterogen eity within this subset was also observed (HLOD 1.21, P = .02), with simila r to 20% of families linked. Although not statistically significant, sugges tive evidence for linkage to PCAP was observed for the families (n = 21) th at met the three criteria of male-to-male transmission, average age of diag nosis <66 years, and greater than or equal to 5 affected individuals (maxim um multipoint NPL 1.45, P = .08). There was no evidence for linkage to CAPB in the brain cancer-prostate cancer subset. These results strengthen the a rgument that prostate cancer is a heterogeneous disease and that multiple g enetic and environmental factors may be important for its etiology.