A genome screen of multiplex sibships with prostate cancer

Analysis of a genome screen of 504 brothers with prostate cancer (CaP) who were from 230 multiplex sibships identified five regions with nominally pos itive linkage signals, on chromosomes 2q, 12p, 15q, 16p, and 16q. The stron gest signal in these data is found on chromosome 16q, between markers D16S5 15 and D16S3040, a region suspected to contain a tumor-suppressor gene. On the basis of findings from previous genome screens of families with Cap, th ree preplanned subanalyses were carried out, in the hope of increasing the subgroup homogeneity. Subgroups were formed by dividing the sibships into a group with a positive family history (FH+) that met criteria for "heredita ry" Cap (n = 111) versus those which did not meet the criteria (n = 119) an d by dividing the families into those with a mean onset age below the media n (n = 115) versus those with a mean onset age above the median (n = 115). A separate subanalysis was carried out for families with a history of breas t cancer (CaB+ [n = 53]). Analyses of these subgroups revealed a number of potentially important differences in regions that were nonsignificant when all the families were analyzed together. In particular, the subgroup withou t a positive family history (FH -) had a signal in a region that is proxima l to the putative site of the HPC1 locus on chromosome 1, whereas the late- age-at-onset group had a signal on 4q. The CaB+ subgroup revealed a strong linkage signal at 1p35.1.