Linkage of prostate cancer susceptibility loci to chromosome 1

Three prostate cancer susceptibility genes have been reported to be linked to different regions on chromosome 1: HPC1 at 1q24-25, PCAP at 1q42-43, and CAPB at 1p36. Replication studies analyzing each of these regions have yie lded inconsistent results. To evaluate link age across this chromosome syst ematically, we performed multipoint linkage analyses with 50 microsatellite markers spanning chromosome 1 in 159 hereditary prostate cancer families ( HPC), including 79 families analyzed in the original report describing HPC1 linkage, The highest lod scores for the complete dataset of 159 families w ere observed at 1q24-25 at which the parametric lod score assuming heteroge neity (hlod) was 2.54 (P=0.0006) with sin allele sharing lod of 2.34 (P=0.0 01) at marker D1S413, although only weak evidence was observed in the 80 fa milies not previously analyzed for this region (hlod-0.44, P=0.14, and alle le sharing lod=0.67, P=0.08). In the complete data set, the evidence for li nkage across this region was very broad, with allele sharing lod scores gre ater than 0.5 extending approximately 100 cM from 1p13 to 1q32, possibly in dicating the presence of multiple susceptibility genes. Elsewhere on chromo some 1, some evidence of linkage was observed at 1q42-43, with a peak allel e sharing lod of 0.56 (P=0.11) and hlod of 0.24 (P=0.25) at D1S235. For ana lysis of the CAPB locus at 1p36, we focused on six HPC families in our coll ection with a history of primary brain cancer; four of these families had p ositive linkage results at 1p36, with a peak allele sharing lod of 0.61 (P= 0.09) and hlod of 0.39 (P=0.16) at D1S407 in all six families. These result s are consistent with the heterogeneous nature of hereditary prostate cance r, and the existence of multiple loci on chromosome 1 for this disease.